KR100861171B1 - Compositions for the preparation of carbon dioxide gel for external use and carbon dioxide gels for external use - Google Patents

Abstract

The composition for preparing carbon dioxide external gel of the present invention is used to prepare a carbon dioxide external gel obtained by dissolving carbon dioxide in a gel in a substantially non-bubble state, and comprises a granular material and a viscous material mixed with the granular material. In the first composition for preparing carbon dioxide external gel, the granular material includes a weak acid and a calcium ion trapping agent as essential components, and the viscous substance includes a gelling agent and water gelled by calcium carbonate and calcium ions as essential components. . In addition, as a second composition for preparing carbon dioxide external gel, the granular material includes a weak acid and a dispersant as essential ingredients, and a gelling agent, a calcium ion scavenger, and water, in which the viscous material is gelled with calcium carbonate and calcium ions, are essential. It is made with an ingredient.

Carbon dioxide external gel, granule, viscous substance, calcium ion trapping agent

Description

Compositions for the preparation of carbon dioxide gel for external use and carbon dioxide gels for external use}

The present invention relates to a composition for preparing a carbon dioxide external gel for preparing a carbon dioxide external gel which can easily obtain a cosmetic or medical effect by external application of carbon dioxide, and a carbon dioxide external gel obtained thereby.

Carbon dioxide absorbed by transdermal mucosal membranes promotes blood circulation in the skin, subcutaneous tissues and muscles and activates metabolism to obtain cosmetic or medical effects. It is clear from the point which has been made and various studies. For example, as a medical effect, Hiyoshi et al. Have reported that artificial carbonated springs are effective against intractable pressure sores (Hiyoshi Toshinori; treatment of pressure sores by artificial carbonated springs.) 8): 605-609, 1989).

In order to easily obtain cosmetic or medical effects by external use of carbon dioxide, a carbon dioxide external preparation containing carbon dioxide or an external preparation which generates carbon dioxide by a prepared preparation (as prepared on an as-needed basis) has been proposed. The external carbon dioxide has a problem in that its manufacturing technology is not established, the loss of carbon dioxide is low, or the price of a storage container with low loss is high. There are fewer problems and more practical. As a composition which can prepare such an external preparation, for example, the composition preparation kit for carbon dioxide transdermal and transmucosal absorption (refer to Unexamined-Japanese-Patent No. 2000-319187), or the composition for external preparation of carbon dioxide (refer to WO02 / 80941) is proposed. have.

In Japanese Patent Application Laid-Open No. 2000-319187 or WO02 / 80941, transdermal and transmucosal absorption of carbon dioxide, athlete's foot, insect bites, atopic dermatitis, molecular eczema, dry skin, seborrheic eczema, dungjin, Yangjin, housewife Skin mucosal disorders or skin mucosal disorders such as eczema, acne acne, impetigo, blepharitis, carbuncle, extinction, cellulitis, pyoderma, psoriasis, young line, palmar keratokeratosis, mammary gland, nasal eruption, wound, laceration, crack, erosion, frostbite Skin mucosal damage such as itching, pressure sores, wounds, lacerations, stomatitis, stomatitis, skin ulcers, cracks, erosions, frostbite, gangrene; Engraftment failure of transplanted skin fragments, skin lesions, etc .; Dental diseases such as gingivitis, alveolar pylori, denture ulcer, bleached gingival, stomatitis; Skin ulceration, cold feeling, and pickling based on peripheral circulatory disorders such as obstructive thrombitis, obstructive arteriosclerosis, diabetic peripheral circulation disorder, and varicose veins; Musculoskeletal disorders such as chronic rheumatoid arthritis, dog shoulder syndrome, myalgia, arthralgia, back pain; Nervous system diseases such as neuralgia, multiple neuritis, and suvacute myelo-optico-neuropathy; Keratose disorders such as psoriasis, corn, callus, young gland, palmar paw keratosis, thyroid, nasal gangrene; Purulent skin diseases such as acne vulgaris, impetigo, hair follicles, carbuncles, incisions, cellulitis, pyoderma, purulent eczema; Inhibit hair regrowth after depilation (unnecessary hair treatment); It is disclosed that it is effective for cosmetic problems such as freckles, rough skin, dull skin, reduction of skin elasticity and skin gloss, reduction of hair gloss, and cosmetic problems and partial obesity.

By the way, it is known that carbon dioxide is hardly absorbed by the transdermal mucosal membrane in gas phase normally. For example, carbonic acid springs exhibit medical and cosmetic effects such as increased blood pressure, pressure sores, and skin roughening. Carbon dioxide dissolved in water from carbonated springs is absorbed by transdermal transmucosal membranes (Isa Nagakura; Carbonic Acid Gas, Maintaining Life). Mysterious substance, see Asahi Shimbun published). Therefore, in order to produce the cosmetic or medical effect, it is necessary to dissolve carbon dioxide in a solvent such as water.

Since the kit of Unexamined-Japanese-Patent No. 2000-319187 uses a bubble carbon dioxide, even if the obtained composition is apply | coated to skin mucosa, the efficiency of transdermal transmucosal absorption is not high. For this reason, in order to fully acquire the cosmetic or medical effect, long-term continuous use is required. Specifically, face slimming requires two weeks to two months of daily use. In addition, since bubble carbon dioxide forms unnecessary voids in the composition obtained by said kid, the said carbon dioxide is not used for percutaneous transmucosal absorption. At the same time, there is a drawback that the fluidity of the whole becomes high, and it flows down from the coated surface to pollute clothes and the like. Moreover, since the composition obtained by the said kit is a viscous substance, face wash etc. are needed at the time of removal after use, and it cannot be said that it is convenient to use.

On the other hand, the composition of WO02 / 80941 almost eliminates the drawbacks of the kit of Japanese Patent Laid-Open No. 2000-319187, but it is also necessary to wash the face when removed after use, which is not necessarily convenient. . In addition, although a stronger cosmetic or medical effect is obtained in a shorter time than the kit, further improvement is desired in terms of effects.

The present invention has been made in view of the above circumstances, and a composition for preparing a carbon dioxide external gel for preparing a carbon dioxide external gel which has a stronger cosmetic or medical effect in a shorter time, and which does not flow when applied, and which is easy to remove after use, is easy to use. And the carbon dioxide external gel obtained thereby.

The present inventors earnestly studied about the carbon dioxide external preparation which can obtain a stronger cosmetic or medical effect. In the process, it was conceived to obtain a stronger cosmetic or medical effect by gelling with a cation released from carbonate, a raw material of carbon dioxide, and also absorbing non-bubble carbon dioxide in a transdermal mucosa. However, experiments have been repeated. Carbon dioxide rapidly reacts with carbonates and acids, and the reaction between cations released from carbonates and gelling agents is also rapid, resulting in the formation of carbon dioxide in the gel or in the air. Furthermore, knowledge has been obtained that there is a problem such as generation of carbon dioxide before gelation is completed, depending on the type of raw materials, the blending ratio, and the like. Therefore, the present inventors have completed the present invention as a result of repeated experiments focused on solving the problem by slowing down the generation and dissolution rate of carbon dioxide and the reaction rate of the gelling agent, and by tuning the speeds of both.

That is, the 1st carbon dioxide external gel preparation composition of this invention is used for preparation of the carbon dioxide external gel which melt | dissolves carbon dioxide in a gel in a substantially non-bubble state, The following granular material (A) and this granular material It consists of the viscous substance (B) mixed with (A).

(A) Granular material which contains a weak acid and a calcium ion trapping agent as an essential component.

(B) Calcium carbonate, a gelling agent gelling with calcium ions, and a viscous substance having water as an essential component.

Here, the gel in the present invention means that a polymer or the like swollen with a solvent such as water forms a three-dimensional network structure, and it is difficult to trap a large number of solvent molecules in the network structure.

In addition, the substantially non-bubble state referred to in the present invention refers to a state in which the carbon dioxide on the bubble is hardly recognized visually.

In addition, the granular material referred to in the present invention means any one of solids such as powder, fine grains, granules and microcapsules or a mixture of these solids.

In addition, the calcium ion trapping agent referred to in the present invention means that the gelation rate and the curing rate of the gel can be controlled by combining with calcium ions and gelling with calcium ions.

According to the first composition for preparing carbon dioxide external gel for carbon dioxide, when the particulate matter (A) and the viscous material (B) are mixed, the weak acid in the particulate material (A) and calcium carbonate in the viscous material (B) react to form carbon dioxide. At the same time, a gelling agent (hereinafter, simply referred to as a "gelling agent") gelling with calcium ions in the viscous substance (B) by the calcium ions released from the calcium carbonate gels to cure the gel. At this time, since the calcium ion trapping agent traps calcium ions, the rapid progress of gelation is suppressed. In addition, since the calcium ion trapping agent in the granular material (A) acts to slow the contact between the weak acid and calcium carbonate during the mixing of the granular material (A) and the viscous material (B), carbon dioxide is also suddenly generated. Suppressed. For this reason, before a carbon dioxide melt | dissolves in a non-bubble state, a gel hardens | cures, a carbon dioxide generate | occur | produces rapidly, and the carbon dioxide of a bubble remains in a gel, or the generated carbon dioxide disperse | disperses in air | atmosphere effectively. Therefore, a carbon dioxide external gel in which carbon dioxide in a substantially non-bubble state is dissolved in a gel can be obtained. In addition, according to such a carbon dioxide external gel, the amount of carbon dioxide percutaneous transdermal mucosa is large, and thus a stronger cosmetic or medical effect can be effectively obtained. Moreover, since it is a gel, it is hard to flow from the skin mucous membrane. Furthermore, by adjusting the compounding ratio of the raw materials, the gel is cured after a certain time has elapsed after preparation and can be easily peeled off from the skin mucosa.

In the first composition for preparing carbon dioxide external gel for carbon dioxide, it is preferable that the calcium ion trapping agent of the granular material (A) is at least one of sodium ethylenediamine tetraacetate and glycine. In this case, since calcium ions are captured more effectively, the rapid progress of gelation is effectively suppressed. Therefore, according to the carbon dioxide external gel obtained by the composition for preparing carbon dioxide external gel, a stronger cosmetic or medical effect can be obtained more effectively.

In the first carbon dioxide external gel preparation composition, the weak acid of the granular material (A) is at least one of sodium dihydrogen phosphate and potassium dihydrogen phosphate, and the calcium ion trapping agent of the granular material (A) is ethylene. It is preferable that the gelling agent which is at least one of diamine disodium acetate and glycine, and gelatinized by calcium ion of the said viscosity (B) is sodium alginate. In this case, the carbon dioxide external gel in which carbon dioxide in a substantially non-bubble state is dissolved is easily prepared. In addition, the end time of the generation and dissolution of carbon dioxide and the end time of the reaction of the gelling agent are almost the same, which has the advantage of obtaining a carbon dioxide external gel in which a stronger cosmetic or medical effect can be obtained more effectively. Furthermore, the carbon dioxide external gel which is hard to flow out from the skin mucosa is easily obtained, and when adjusting the blending ratio of the raw material, etc., the carbon dioxide external gel can be easily obtained by curing at a predetermined time after preparation and easily peeling off.

Moreover, in the said 1st carbon dioxide external gel preparation composition, it is preferable that the said granular material (A) also contains a dispersing agent. In this case, when the particulate matter (A) is dissolved in the viscous material (B), the contact between the weak acid and calcium carbonate is suppressed, so that the generation rate of carbon dioxide can be further suppressed. For this reason, the generated carbon dioxide does not bubble in the gel or disperse in the air, but immediately dissolves in the gel in a substantially non-bubble state. At the same time, since the glass speed of calcium ions liberated from calcium carbonate is also suppressed, the gelling agent gels and hardens at an appropriate speed. For this reason, when the carbon dioxide external gel is prepared using the granular material (A) and the viscous material (B), a gel that gradually hardens is formed, and the required amount of carbon dioxide is dissolved in the gel in a substantially non-bubble state. . Therefore, when the particulate matter (A) is mixed with the viscous material (B) and applied to the skin mucous membrane, carbon dioxide in a substantially non-bubble state is absorbed by the transdermal mucosa, thereby obtaining a strong cosmetic or medical effect. Moreover, since the carbon dioxide external gel obtained is a gel, it is hard to flow from a skin mucosa. Furthermore, by adjusting the compounding ratio of the raw materials, it is cured after a certain time has elapsed after preparation and can be easily peeled off from the skin mucosa.

Moreover, in the said 1st carbon dioxide external gel preparation composition, it is preferable that the said granular material (A) contains a dispersing agent and a binder further. In this case, when the granular material A and the viscous material B are mixed, the collapse control of the granular material A is better performed, so that the dissolution rate of the granular material A is moderate. Therefore, according to the carbon dioxide external gel obtained by the composition for preparing carbon dioxide external gel, a stronger cosmetic or medical effect can be obtained more effectively.

Moreover, in the said 1st carbon dioxide external gel preparation composition, it is preferable that the said viscosity substance (B) contains the adhesive for improving affinity with the skin mucosal surface further. In this case, the mixture of the granular material (A) and the viscous material (B) is more difficult to flow down in close contact with the skin mucosa, which has the advantage that the percutaneous transmucosal absorption of carbon dioxide is performed more efficiently.

Moreover, in the said 1st carbon dioxide external gel preparation composition, it is preferable that the said viscosity thing (B) contains alcohol further. In this case, there is an advantage that the spreadability of the viscous substance B is improved and the usability is also improved.

Moreover, in the said 1st carbon dioxide external gel preparation composition, it is preferable that the average particle diameter of the said granular material (A) is set to the range of 0.05-1.0 mm. In this case, when the granular material (A) and the viscous material (B) are mixed, the dissolution rate of the granular material (A) becomes moderate, and the end time of the generation and dissolution of carbon dioxide and the end of the reaction of the gelling agent Time becomes even more the same.

The second composition for preparing carbon dioxide external gel of the present invention is used to prepare a carbon dioxide external gel obtained by dissolving carbon dioxide in a gel in a substantially non-bubble state, and the following granular material (X) and the granular material (X) It is characterized by consisting of a viscous substance (Y) to be mixed with.

(X) Granular material which contains weak acid and a dispersing agent as an essential component.

(Y) A viscous substance comprising calcium carbonate, a gelling agent gelled with calcium ions, a calcium ion trapping agent, and water as essential ingredients.

Here, the dispersing agent as used in this invention means disperse | distributing raw materials, such as a weak acid, in a granular material, slowing release of the weak acid from a granular material suitably, and dissolving or swelling in water at an appropriate speed | rate.

According to the composition for preparing the second carbon dioxide external gel, similarly to the first composition for preparing the external carbon dioxide external gel, when the particulate matter (X) and the viscous material (Y) are mixed, the weak acid in the particulate matter (X) and Calcium carbonate in the viscous substance (Y) reacts to generate carbon dioxide, and the gelling agent in the viscous substance (Y) gels with calcium ions released from the calcium carbonate to cure the gel. At this time, since the weak acid in the granular material X dissolved by the viscous substance Y is slow in contact with calcium carbonate by the dispersant, the generation of carbon dioxide is delayed, and the calcium ion trapping agent traps calcium ions. Rapidly gelling is suppressed. Therefore, a carbon dioxide external gel in which much carbon dioxide in a substantially non-bubble state is dissolved can be obtained. In addition, according to such a carbon dioxide external gel, since the transdermal mucosal absorption amount of carbon dioxide is large, a stronger cosmetic or medical effect can be obtained in a shorter time. In addition, it is difficult to flow from the skin mucosa because it is a gel. Furthermore, by adjusting the compounding ratio of the raw materials, the gel is cured after a certain time has passed after preparation, and can be easily peeled off from the skin mucosa.

In the second composition for preparing carbon dioxide external gel, the calcium ion trapping agent of the particulate matter (X) is preferably disodium hydrogen phosphate. In this case, since calcium ions are captured more effectively, the rapid progress of gelation is suppressed more effectively. Therefore, according to the carbon dioxide external gel obtained by the composition for preparing carbon dioxide external gel, a stronger cosmetic or medical effect can be obtained more effectively.

In the second composition for preparing carbon dioxide external gel, the weak acid of the granular material (X) is at least one of sodium dihydrogen phosphate and potassium dihydrogen phosphate, and gelled with calcium ions of the viscous product (Y). It is preferable that the gelling agent to be mentioned is sodium alginate, and the calcium ion trapping agent of the said viscous substance (Y) is disodium hydrogen phosphate. In this case, it is easy to prepare a carbon dioxide external gel in which carbon dioxide in a substantially non-bubble state is dissolved. In addition, the end time of the generation and dissolution of carbon dioxide and the end time of the reaction of the gelling agent are almost the same, which has the advantage of reliably obtaining a carbon dioxide external gel obtained in a shorter time with a stronger cosmetic or medical effect. Moreover, the carbon dioxide external gel which is hard to flow from the skin mucosa is easily obtained, and when the blending ratio of the raw material is adjusted, the carbon dioxide external gel can be easily obtained by curing after a preparation for a certain time and easily peeling off. Have

Moreover, in the said 2nd carbon dioxide external gel preparation composition, it is preferable that the said granular material (X) contains a binder further. In this case, when the said granular material X and the said viscous material Y are mixed, it will be used together with the dispersing agent in the said granular material X, and control of collapse of the granular material X will be performed more favorably, and the said granular material ( The dissolution rate of X) becomes moderate. Therefore, according to the carbon dioxide external gel obtained by the composition for preparing carbon dioxide external gel, a stronger cosmetic or medical effect can be obtained more effectively.

Moreover, in the said 2nd carbon dioxide external gel preparation composition, it is preferable that the said viscosity substance (Y) contains the adhesive for improving affinity with the skin mucosal surface further. In this case, mixing of the granular material X and the viscous material Y is difficult to flow further down the skin mucosa, so that transdermal transmucosal absorption of substantially non-bubble carbon dioxide is performed more efficiently. Has an advantage.

Moreover, in the said 2nd carbon dioxide external gel preparation composition, it is preferable that the said viscous substance (Y) contains alcohol further. In this case, it has the advantage that the spreadability of the said viscous substance Y improves, and a usability also improves.

Moreover, in the said 2nd carbon dioxide external gel preparation composition, it is preferable that the average particle diameter of the said granular material (X) is set to the range of 0.05-1.0 mm. In this case, when the granular material (X) and the viscous material (Y) are mixed, the dissolution rate of the granular material (X) becomes moderate, and the end time of the generation and dissolution of carbon dioxide and the end time of the reaction of the gelling agent It becomes more similar than this.

The carbon dioxide external gel of the present invention is formed using the first and second carbon dioxide external gel preparation compositions, and is characterized in that carbon dioxide is dissolved in the gel in a substantially non-bubble state. According to the above arrangement, since the first and second carbon dioxide external gel preparation compositions capable of suppressing the generation and dissolution rate of carbon dioxide and the reaction rate of the gelling agent are used, a large amount of carbon dioxide in a substantially non-bubble state is used. It becomes the gel which I included. For this reason, the amount of carbon dioxide absorbed by transdermal transmucosal membrane increases, and a stronger cosmetic or medical effect can be obtained. In addition, the carbon dioxide external gel of the present invention has a smaller volume and a higher physical strength than the carbon dioxide external agent having the same weight as the essential component of bubble carbon dioxide when the carbon dioxide content is the same. Therefore, it can apply | coat to thin and uniform thickness on skin mucosa, and has the advantage that strong cosmetic or medical effect can be acquired in a small amount. In addition, since the carbon dioxide external gel of the present invention has a moderate viscosity and adhesiveness and is difficult to flow from the coated surface, a strong cosmetic or medical effect can be obtained without soiling clothes or the like. Furthermore, by adjusting the compounding ratio of the raw materials, the gel is cured after a certain time has passed after preparation, and can be easily peeled off from the skin mucosa.

The wound covering of the present invention is made by using the first and second carbon dioxide external gel preparation compositions, wherein carbon dioxide is dissolved in the gel in a substantially non-bubble state. According to the above structure, since the first and second carbon dioxide external gel preparation compositions which can control the generation / dissolution rate of carbon dioxide and the reaction rate of the gelling agent are used, a large amount of carbon dioxide in a substantially non-bubble state is used. It becomes the gel which I included. For this reason, the amount of carbon dioxide absorbed by transdermal mucosa increases, and the healing effect, such as a wound, by the percutaneous transmucosal absorption of carbon dioxide can be obtained more strongly. In addition, when the carbon dioxide external gel obtained by the first and second carbon dioxide external gel preparation compositions is applied to a wound or the like to form a hydrogel and then directly attached to the skin mucosa without peeling and removing, it functions as a protective sheet such as a wound. It has the advantage that it can be done.

Next, this invention is demonstrated dividing into two of the composition for 1st carbon dioxide external gel preparation, and the composition for 2nd carbon dioxide external gel preparation.

[The first carbon dioxide external gel preparation composition]

The 1st carbon dioxide external gel preparation composition which concerns on this embodiment is a granular material (A) which has a weak acid and a calcium ion trapping agent as an essential component, the gelling agent and water which gelate with calcium carbonate and calcium ion as essential components. It consists of viscous substance (B) to be used.

The weak acid constituting the granular material (A) is usually in the range in which the pH of the 1 wt% aqueous solution is 3.0 or more and less than 7.0, and both inorganic and organic acids may be used alone or in combination of two or more. In the case of using a weak acid, if a strong acid is used, even if the amount of the strong acid is reduced, the reaction with calcium carbonate is so fast that carbon dioxide is rapidly generated locally, and the generated carbon dioxide is bubbled in the gel, or is acid in the air. It is because they do it. In addition, since the release of calcium ions is also fast, the reaction rate of the gelling agent can not be sufficiently slowed even by the calcium ion trapping agent, and gels and hardens in a short time. That is, the use of the weak acid is because a large amount of carbon dioxide in a substantially non-bubble state is dissolved in the gel. Especially, the weak acid which has a buffering effect and which acidity does not become strong beyond a certain level even if concentration is high is preferable. More preferably, they are sodium dihydrogen phosphate and potassium dihydrogen phosphate.

And as a compounding quantity of a weak acid, it depends also on the kind of weak acid, etc., Usually, 5-75 weight% is preferable with respect to granular material (A) whole quantity, More preferably, it is 30-50 weight%. If it is less than 5% by weight, depending on the amount of the viscous substance (B) to the granular substance (A), the blending component of the viscous substance (B), the blending ratio, etc., since the amount of carbon dioxide generated and the amount of calcium ion released are small, This is because the amount of dissolved non-bubble carbon dioxide is too small, or gelation is insufficient. On the contrary, if it exceeds 75% by weight, the amount of viscous substance (B) to the granular substance (A), the blending component of the viscous substance (B), the mixing ratio, etc. are large, but since the amount of carbon dioxide generated and the amount of calcium ion released are too large, This is because the carbon dioxide may bubble in the gel, or the gel may harden quickly and the generation of carbon dioxide may stop. That is, it is preferable to keep the compounding amount of the weak acid within the above range because a large amount of non-bubble carbon dioxide can be dissolved in the gel.

As the calcium ion trapping agent constituting the granular material (A), any calcium ion can be used without particular limitation as long as the calcium ion is competitively bonded to the gelling agent. Specifically, disodium hydrogen phosphate, sodium polyphosphate, sodium hexametaphosphate, sodium pyrophosphate, sodium tripolyphosphate, hydroxyethane diphosphonate, hydroxyethylidene diphosphonate, Phosphoric acid or phosphonic acid type calcium ion trapping agents, such as sodium tetrahydroxy phosphide diphosphonic acid, nitrilotris (methylene phosphonate), and phosphonobutane tricarboxylate, and citric acid Carboxylic acid calcium ion trapping agents, such as trisodium acid and sodium gluconate, ethylenediamine tetraacetic acid, ethylenediamine tetraacetic acid, ethylenediamine triacetate, sodium ethylenediamine tetraacetic acid, ethylenediamine tetraacetate, hydroxyethyl ethylenediamine Triacetic acid (hydroxyethyl ethylendiamine triacetate), hydroxyethyl ethylenediamine triacetate Sodium, diethylene triamine OH, diethylene triamine OH, sodium ethylene diamine tetraacetate, nitrilotriacetate, methylglycine diacetate, ethylene diamine hydroxyethyl triacetate trisodium ethylenediamine hydroxyethyltriacetate), dihydroxyethylethylenediaminediacetic acid, propanediamine tetraacetic acid, triethylenetetramine hexaacetic acid, hydroxyethyl iminodiacetate, dicarboxyethyl glutamate sodium sodium diacetate, dihydroxyethylglycine, 1 And aminocarboxylic acid calcium ion trapping agents such as, 3-diamino-2-hydroxypropaneacetic acid, and amino acid calcium ion trapping agents such as glycine. These can be used individually or in combination of 2 or more types. Among them, sodium ethylenediamine tetraacetate and glycine are preferred because they are excellent in controlling calcium ion trapping and re-release, controlling gelation rate and curing rate, and the like.

And as a compounding quantity of a calcium ion trapping agent, although it also depends on the kind of calcium ion trapping agent, etc., 0.5-50 weight% is preferable normally with respect to granular material (A) whole quantity, and 4.0-40 weight% is more preferable. If it is less than 0.5% by weight, depending on the amount of viscous substance (B) to the granular substance (A), the blending component of the viscous substance (B), the blending ratio, and the like, the trapping of calcium ions is insufficient, resulting in rapid gelation and curing of the gel. It is because there is a possibility that generation of carbon dioxide may stop. On the contrary, if it exceeds 50% by weight, the amount of viscous substance (B) to the granular substance (A) or the blending component and blending ratio of the viscous substance (B) also depends, but too much calcium ion is trapped to sufficiently gel and harden the gel. This is because the generated carbon dioxide may bubble in the gel or disperse in the atmosphere.

The granular material (A) containing the weak acid and the calcium ion trapping agent as essential components is, for example, fine grains or granules, and the average particle diameter (half of the sum of the maximum length and the minimum length in one) is 0.05 to 1.0 mm. It is preferable to set in the range of, Especially preferably, it is the range of 0.1-0.3 mm. That is, it is preferable to be smaller than the granular material (refer to WO02 / 80941) of the conventional composition for carbon dioxide external preparation. When the granular material (A) is too large, when mixed with the viscous material (B), it takes a long time to dissolve, making it difficult to proceed with the reaction between the weak acid and calcium carbonate, and as a result, generation of carbon dioxide It is because it may become too late or gelation and gel hardening may not be performed sufficiently. On the contrary, when the granular material (A) is too small, when mixed with the viscous material (B), the granular material (A) immediately dissolves, and the reaction between the weak acid and calcium carbonate tends to proceed too quickly. This is because there is a possibility that carbon dioxide is rapidly generated and carbon dioxide is bubbled in the gel, scattered in the atmosphere, or the calcium ions are released too quickly, causing gelation and curing of the gel rapidly. In addition, it is preferable that the surface of the granular material A has more irregularities than the mirror surface because more uniform collapse and dissolution occur due to contact with the viscous material B.

The granular material (A) is wetted using the above essential components by adding a dispersant used for preventing the reaction of the weak acid and calcium carbonate too fast, a binder used for maintaining the shape of the particles, and the like, if necessary. It can manufacture by employ | adopting a well-known manufacturing method, such as a granulation method and a dry granulation method.

As a dispersing agent, when it is a microparticle, it is comparatively easy to melt | dissolve or swell when it mixes with a viscous substance (B), and it can use without a restriction | limiting especially. For example, alpha starch, starch derivatives such as α-cyclodextrin, sugars such as sucrose, glucose, fructose, sucrose, lactose, xylitol, D-sorbitol, and D-mannitol, pullulan and glass Cellulose derivatives such as polysaccharides such as xanthan gum, hydroxypropylcellulose, hydroxypropylmethylcellulose, carmellose calcium, carmellose sodium, salts thereof, and polyvinylpyrrolidone Synthetic polymers, urea and the like can be used. These can be used individually or in combination of 2 or more types.

Moreover, as a binder, it can use, dissolving or swelling in a suitable solvent as microparticles | fine-particles, and if it can combine two or more substances, it can use without a restriction | limiting in particular. For example, gum arabic, crystalline cellulose, sodium carmellose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose terephthalate, sodium carboxymethyl cellulose, carboxymethyl ethyl cellulose, hydroxyethyl cellulose , Dextrin, wheat starch, rice starch, corn starch, hydroxypropyl starch, alpha starch, pullulan, polyvinylpyrrolidone, methacrylic acid copolymer, polyvinyl alcohol, agar, gelatin, tragacanth gum gum tragacanth, potato starch and the like. These can be used individually or in combination of 2 or more types.

In the granular material (A) thus obtained, the weak acid and the calcium ion trapping agent are preferably dispersed as uniformly as possible. Accordingly, uniformly mixing the granular material (A) and the viscous material (B) suppresses the local increase or decrease of the calcium ion concentration, and the amount of carbon dioxide generated is too much or too little locally. This is because it is suppressed. That is, a carbon dioxide external gel in which a sufficient amount of carbon dioxide is dissolved in a non-bubble state can be obtained.

When the reaction between the weak acid and calcium carbonate is too fast, the granular material (A) is, for example, the surface of the granular material (A) as a delayed raw material (raw material that slows the dissolution rate relative to the viscous material (B)). It is good also as a controlled release granular material which coat | covers and controls release of a weak acid, etc., and may be set as the collapse rate controlled granular material which slowed the decay rate of the granular material A with a binder at the time of manufacture of the granular material A.

On the other hand, the viscous substance (B) used together with the granular substance (A) mentioned above has calcium carbonate as an essential component. Calcium carbonate is used as the carbonate for the following reasons. That is, when using magnesium carbonate, which is a carbonate containing a divalent metal ion equal to calcium carbonate, of course, carbon dioxide is generated by reaction with an acid, but when gelling the gelling agent using magnesium carbonate, the hardness of the gel is lowered. There is this. As a result, carbon dioxide generated in the gel is easily bubbled or dissipated in the air, and thus it is difficult to obtain a carbon dioxide external gel in which carbon dioxide in a substantially non-bubble state is sufficiently dissolved. For this reason, calcium carbonate is used as an essential component as a raw material for the generation of carbon dioxide and the release of divalent metal ions.

As the amount of the calcium carbonate blended, depending on the kind of the weak acid, the gelling agent, the amount of the gelling agent, and the like, the amount is preferably 0.1 to 6.0% by weight, more preferably 0.2 to 2.0% by weight, more preferably 0.2 to 2.0% by weight, based on the total amount of the viscous substance (B). Preferably it is 0.3-1.0 weight%. If it is less than 0.1% by weight, depending on the amount of the granular material (A) to the viscous material (B), the blending component of the granular material (A), the blending ratio, and the like, the amount of carbon dioxide generated is too small or gelation may be insufficient. Because there is. Conversely, if it exceeds 6.0% by weight, depending on the amount of granular material (A) used to the viscous material (B), the blending component of the granular material (A), the blending ratio, etc., generation and dissolution of carbon dioxide when the granular material (A) is mixed This is because the speed is so fast that the generated carbon dioxide may bubble in the gel or disperse in the atmosphere.

The gelling agent constituting the viscous substance (B) can be used without particular limitation as long as it is gelled with calcium ions released from calcium carbonate. For example, carrageenan, demethoxylated pectin, sodium alginate, potassium alginate, ammonium alginate and the like can be used. These can be used individually or in combination of 2 or more types. Especially, sodium alginate is preferable for the reason of being excellent in affinity with the skin mucosa, and feeling of use.

As the blending amount of the gelling agent, depending on the kind of the gelling agent or the like, in general, 0.3 to 15.0% by weight relative to the total amount of the viscous substance (B) is preferable, more preferably 0.3 to 8.0% by weight, still more preferably 1.5 to 5.0 wt%. If the content is less than 0.3% by weight, the amount of the granular material (A) to the viscous material (B) depends on the amount of the granular material (A), the blending component of the granular material (A), the blending ratio, and the like. This is because gelation is insufficient, and the generated carbon dioxide may bubble or disperse in the atmosphere. On the contrary, when it exceeds 15.0 weight%, it depends also on the usage-amount of granular material (A) with respect to a viscous material (B), the compounding component of a granular material (A), a compounding ratio, etc. This is because the viscosity may become too high and further dissolution of the granular material (A) may be difficult, and the reaction of the weak acid with calcium carbonate may be difficult to occur.

As water constituting the viscous substance (B), natural water, tap water, distilled water, purified water and the like are used without particular limitation. Carbon dioxide is dissolved not only in water but also in many solvents including organic solvents and lipids. Among them, water is more likely to react with weak acid and calcium carbonate than organic solvents and lipids. Release of the gelling agent and gelation of the gelling agent easily occur. In addition, water is generally easy to handle, inexpensive and safe. For this reason, water is used as an essential ingredient.

And as a compounding quantity of water, although also according to the kind of other raw materials, compounding quantity, etc., 70-95 weight% is preferable normally with respect to viscous substance (B) whole quantity. It is because when it is less than 70 weight%, a granular material (A) is hard to melt | dissolve and there exists a possibility that reaction of a weak acid and calcium carbonate will not occur easily. On the contrary, when it exceeds 95 weight%, since the compounding quantity of another essential component is too small, when granular material (A) is mixed, gelation and hardening of a gel may become inadequate or the generation amount of carbon dioxide may become inadequate.

The viscous substance (B) containing calcium carbonate, a gelling agent and water as essential components has a viscosity such that the granular substance (A) is evenly spread when mixed with the granular substance (A), and can be easily uniformly dispersed. It is desirable to have. In addition, when the particulate matter (A) and the viscous material (B) are mixed and then directly applied to the skin mucosa and used, it is preferable to have a viscosity that does not flow down from the skin mucosa immediately after mixing.

A viscous substance (B) can be manufactured by adding and mixing to the said essential component the adhesive (henceforth simply a "sticker" hereafter) etc. for improving affinity with the skin mucosal surface as needed.

Examples of the pressure-sensitive adhesive include gum arabic, crystalline cellulose, sodium carmellose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose terephthalate, sodium carboxymethyl cellulose, carboxymethyl ethyl cellulose, and hydroxy. Oxyethylcellulose, dextrin, wheat starch, rice starch, corn starch, hydroxypropyl starch, alpha starch, pullulan, polyvinylpyrrolidone, methacrylic acid copolymer, polyvinyl alcohol, gelatin, tragacanth gum, potato starch Minutes and agar can be used. These can be used individually or in combination of 2 or more types.

And although it depends also on the kind of adhesive etc. as a compounding quantity of an adhesive, 0.1-5.0 weight% is preferable normally with respect to viscous substance (B) whole quantity. If it is less than 0.1% by weight, the adhesive force is insufficient, and this is because there is little meaning to mix. On the contrary, when it exceeds 5.0 weight%, since adhesive force is too strong and it may become difficult to remove from the skin mucous membrane after use.

The 1st composition for carbon dioxide external gel preparation which consists of the said granular material (A) and viscous material (B) can be used as follows, for example. That is, first, the granular material A and the viscous material B are mixed in various containers in a predetermined ratio. The ratio of both is preferably set such that calcium carbonate reacts with the weak acid. However, the reaction between calcium carbonate and the weak acid is so fast that the gelation and curing of the gel proceed rapidly, or the carbon dioxide is generated so rapidly that the carbon dioxide bubbles in the gel or disperses in the atmosphere. It is not preferable to use much for the viscous substance (B). More specifically, when the molar ratio of the weak acid of the particulate matter (A) and the calcium carbonate of the viscous material (B) is 0.1% by weight of calcium carbonate, about 0.4 to 40 is preferable, and 0.3% by weight of calcium carbonate In the case of blending, about 0.04-3.6 is preferable, and in the case of blending 6.0 wt% of calcium carbonate, about 0.02-0.54 is preferable. Immediately thereafter, the obtained mixture is applied to a predetermined portion of the skin mucosa. At this time, a carbon dioxide external gel in which carbon dioxide generated by the reaction of weak acid and calcium carbonate is dissolved in the gel in a substantially non-bubble state is obtained, and the carbon dioxide is absorbed into the transmucosal mucosa of the skin mucosa, thereby obtaining a strong cosmetic or medical effect. . In addition, when the compounding ratio of the raw material is adjusted, the gel hardens when a certain time elapses after preparation, so that the gel can be easily removed from the skin mucosa.

Moreover, the raw material normally used for external preparations or cosmetics, for example a fragrance | flavor, a pigment, surfactant, an oil, a humectant, in at least one of a granular material (A) and a viscous material (B) in the range which does not impair the effect of this invention. Thickening agents, alcohols, preservatives, antioxidants, coloring agents, ultraviolet absorbers and scattering agents, drugs and the like may be blended as necessary. Thereby, the carbon dioxide external gel obtained can be used suitably as a cosmetics or external medicine. Especially, it is preferable to use alcohol with respect to a viscous substance (B) for the reason that the usability improves that the spreadability of a gel improves. Moreover, in order to improve the viscosity and adhesiveness of a gel, it is preferable to use a thickener with respect to at least one of a granular material (A) and a viscous material (B).

Examples of the alcohols include monohydric alcohols such as ethanol, propanol, isopropanol, butanol, 1,3-butylene glycol, xylitol, glycerol, sorbitol, propylene glycol, dipropylene glycol, hexylene glycol, pentylene glycol, Polyhydric alcohols, such as polyethyleneglycol, can be used. These can be used individually or in combination of 2 or more types. Especially, 1, 3- butylene glycol, propylene glycol, pentylene glycol, glycerol, and polyethylene glycol are preferable.

As the thickener, natural polymers, semi-synthetic polymers, synthetic polymers, and inorganic substances as shown below can be used. These can be used individually or in combination of 2 or more types.

Natural polymers: gum arabic, galactan, agar, quince seed gum, guar gum, tragacanth gum, pectin, mannan, locust bean gum, Plant-based polymers such as rice starch, wheat starch, corn starch, potato starch, microorganisms such as curdlan, xanthan gum, succinoglucan, dextran, hyaluronic acid and pullulan Protein-based polymers such as albumin, albumin, casein, collagen, gelatin, fibroin and the like.

Semi-synthetic polymer: ethyl cellulose, processed starch, carboxymethyl cellulose and its salts, carboxymethyl ethyl cellulose and its salts, carboxymethyl starch and its salts, croscarmellose and its salts, crystalline cellulose, cellulose acetate, phthalic acid acetate Cellulose polymers such as cellulose, hydroxyethyl cellulose, hydroxypropyl starch, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose phthalate, powdered cellulose, methyl cellulose and methyl hydroxypropyl cellulose, and alpha starch Starch polymers such as partially alpha starch, carboxymethyl starch, dextrin and methyl starch; other polysaccharide polymers such as sodium chondroitin sulfate and sodium hyaluronate.

Synthetic polymer: Carboxyvinyl polymer, sodium polyacrylate, polyvinylacetal diethylaminoacetate, polyvinyl alcohol, polyvinylpyrrolidone, methacrylic acid-ethyl acrylate copolymer, meta Ethyl methacrylate-ethyl methacrylate copolymer, ethyl methacrylate methacrylate trimethylammonium ethyl copolymer, dimethyl amino ethyl methacrylate methyl methyl acrylate copolymer, etc.

Minerals: Hydrous silicon dioxide, light silicic anhydride, colloidal alumina, bentonite, laponite, and the like.

In addition, in the composition for carbon dioxide external gel preparation according to the present embodiment, the granular material (A) and the viscous material (B) may be stored in a substantially non-contacting state until use, and is preferably stored in a closed state. Do. The storage container can be used without any particular limitations such as material, shape and structure. For example, the material may be plastic, glass, aluminum, paper, various polymers or composites of these materials. A cup, a tube, a bag, a bottle, a stick, a pump, etc. are mentioned, Any one of these can be used without a restriction | limiting in particular.

[2nd carbon dioxide composition for external gel preparation]

The 2nd carbon dioxide external gel preparation composition which concerns on this embodiment contains the granular material (X) which has a weak acid and a dispersing agent as an essential component, the gelling agent, calcium ion trapping agent, and water which gelatinize with calcium carbonate and calcium ion, and water. It consists of the viscosity substance (Y) which becomes an essential component. That is, as compared with the first composition for preparing carbon dioxide external gel, a calcium ion trapping agent is used as an essential component in the viscous substance (Y) rather than the granular substance (X), and the dispersant is used as the essential component in the granular substance (X). The point of use is different. In such a configuration, when a calcium ion scavenger is included in the viscous substance (Y), when the particulate matter (X) consisting of a weak acid and the viscous substance (Y) are mixed, the weak acid is evenly distributed throughout the viscous substance (Y). The reason for this is that the reaction between the weak acid and calcium carbonate proceeds rapidly locally before it spreads, and gelation and curing of the gel are performed locally, or the generated carbon dioxide is locally distributed.

The weak acid constituting the granular material (X), like the first carbon dioxide external gel preparation composition, generally refers to a pH in a range of 3.0% to 7.0% of a 1% by weight aqueous solution, and both inorganic and organic acids alone or in combination of two or more. It is available. Using a weak acid is the same reason as the composition for 1st carbon dioxide external gel preparation. Among the weak acids, it has a buffering effect, and even if the concentration is high, the acidity is preferably not stronger than a certain level. More preferably, they are sodium dihydrogen phosphate and potassium dihydrogen phosphate.

And as a compounding quantity of a weak acid, it depends also on the kind of weak acid, etc., Usually, 10-75 weight% is preferable with respect to granular material (X) whole quantity, More preferably, it is 10-60 weight%, More preferably, it is 20-50 weight %to be. That is, it is preferable that it is slightly less than the composition for preparation of the first carbon dioxide external gel. It is preferable that the above range is less than 10% by weight depending on the amount of the viscous substance (Y) to the granular substance (X), the blending component of the viscous substance (Y), the blending ratio, and the like. It is because there is a possibility that the amount of carbon dioxide in the non-bubble state melt | dissolved in the gel is too small, or gelatinization may become inadequate because of the small amount of emitted. On the contrary, when it exceeds 75% by weight, the amount of viscous substance (Y) to the granular substance (X), the blending component of the viscous substance (Y), the mixing ratio, etc. are large, but since the generation amount of carbon dioxide and the emission of calcium ions are too large, This is because there is a risk that carbon dioxide will bubble in the gel, or the gel will harden quickly and the generation of carbon dioxide may stop. That is, it is preferable to make the compounding quantity of a weak acid into the said range because many carbon dioxide of a non-bubble state can be dissolved in a gel.

As a dispersing agent which comprises granular material (X), if it is a microparticle, it is comparatively easy to melt | dissolve or swell when mixed with the viscous material (Y), and it can disperse | distribute another raw material, It can use without a restriction | limiting in particular. Here, the dispersant in the granular material (X) as an essential component is a weak acid and a point in the granular material (X) which does not contain a calcium ion trapping agent when the granular material (X) is dissolved in the viscous material (Y). This is because the calcium carbonate in the substance Y is prevented from contacting at an early stage. Examples of such dispersants include starch derivatives such as alpha starch, α-cyclodextrin, sugars such as sucrose, glucose, fructose, sucrose, lactose, xylitol, D-sorbitol, and D-mannitol, flulan, and xanthan gum. Cellulose derivatives such as polysaccharide, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carmellose calcium, sodium carmellose, salts thereof, synthetic polymers such as polyvinylpyrrolidone, and urea. These can be used individually or in combination of 2 or more types.

And as a compounding quantity of a dispersing agent, although it depends also on the kind, compounding quantity, etc. of weak acid, 10-90 weight% is preferable with respect to granular material (X) whole quantity, and 20-40 weight% is more preferable. If it is less than 10% by weight, depending on the amount of the viscous substance (Y) to the granular substance (X), the blending component of the viscous substance (Y), the blending ratio, and the like, the local concentration of the weak acid when mixed with the viscous substance (Y) is determined. This is because the reaction with calcium carbonate is so high that it suddenly occurs in a part of the viscous substance (Y) and terminates, and the whole may not gel. Conversely, if it exceeds 90% by weight, depending on the amount of the viscous substance (Y) to the granular substance (X), the blending component of the viscous substance (Y), the mixing ratio, and the like, the local concentration of the weak acid when mixed with the viscous substance (Y) Is too low, because the amount of carbon dioxide and the amount of calcium ions generated by the reaction with calcium carbonate are insufficient, so that a sufficient amount of carbon dioxide does not dissolve in a non-bubble state or because the gelation does not proceed sufficiently, This is because there is a fear of being scattered in the air.

The granular material (X) containing the weak acid and the dispersant as essential components is, for example, fine grains and granules, and the average particle diameter (half of the sum of the maximum length and the minimum length in one) is in the range of 0.05 to 1.0 mm. It is preferable that it is set, Especially preferably, it is the range of 0.1-0.3 mm. That is, it is preferable to be smaller than the granular material (refer to WO02 / 80941) of the conventional composition for carbon dioxide external preparation. If the granular material (X) is too large, when mixed with the viscous material (Y), it takes a long time to dissolve and the reaction between the weak acid and calcium carbonate tends to be difficult to proceed, and as a result, the generation of carbon dioxide is too large. This is because there is a fear that the gelation and curing of the gel may not be performed sufficiently. On the contrary, when the particulate matter X is too small, when mixed with the viscous substance Y, the particulate matter X immediately dissolves, and the reaction between the weak acid and calcium carbonate tends to proceed too quickly. This is because carbon dioxide is rapidly generated and carbon dioxide bubbles in the gel, scatters in the atmosphere, or the release of calcium ions is too fast, causing gelation and curing of the gel rapidly. In addition, it is preferable that the surface of the granular material X has more unevenness than the mirror surface because more uniform collapse and dissolution occur due to contact with the viscous water (Y).

The granular material (X) can be produced by employing a known production method such as a wet granulation method or a dry granulation method, by adding a binder or the like used for maintaining the shape of the particles, if necessary, to the essential components. Can be. As a binder, the same thing as the said 1st carbon dioxide external gel preparation composition can be used.

In the particulate matter (X) thus obtained, the weak acid and the dispersant are preferably dispersed as uniformly as possible. As a result, when the particulate matter (X) and the viscous substance (Y) are uniformly mixed, the calcium ion concentration is locally increased or decreased, and the amount of carbon dioxide generated is too much or too little. Because work is suppressed. That is, a carbon dioxide external gel in which a sufficient amount of carbon dioxide is dissolved in a non-bubble state can be obtained.

In addition, when the reaction between the weak acid and calcium carbonate is too fast, the granular material (X) causes the surface of the granular material (X), for example, to slow down the dissolution rate relative to the delaying raw material (the viscous material (Y)). It may be a release controlled granular material which is coated with a gas and suppresses the release of weak acid or the like, or a decay rate controlled granular material which slows the disintegration rate of the granular material X by using a binder during the preparation of the granular material X. .

On the other hand, the viscous substance Y used together with the granular substance X mentioned above has disintegrated calcium as an essential component. The use of calcium carbonate as the carbonate is the same reason as that of the first carbon dioxide external gel preparation composition. As the blending amount of calcium carbonate, depending on the kind of the weak acid, the gelling agent, the blending amount, etc., usually 0.1 to 6.0% by weight relative to the total amount of the viscous substance (Y) is preferable, more preferably 0.2 to 2.0% by weight, more preferably Preferably it is 0.3-1.0 weight%. If it is less than 0.1% by weight, the amount of particulate matter (X) to viscous material (Y), the blending component of granular material (X), the blending ratio and the like are also dependent, but the amount of carbon dioxide generated is too small or gelation may be insufficient. Because there is. Conversely, if it exceeds 6.0% by weight, depending on the amount of the granular material (X) used relative to the viscous material (Y), the blending component of the granular material (X), the blending ratio, and the like, generation and dissolution of carbon dioxide when the granular material (X) is mixed This is because the speed is so fast that the generated carbon dioxide may bubble in the gel or disperse in the atmosphere.

As the gelling agent constituting the viscous substance (Y), like the first composition for preparing carbon dioxide external gel, any gelling agent using calcium ions released from calcium carbonate can be used without particular limitation. For example, carrageenan, low methoxylated pectin, sodium alginate, potassium alginate, ammonium alginate and the like can be used. These can be used individually or in combination of 2 or more types. Especially, sodium alginate is preferable for the reason of being excellent in affinity with the skin mucosa, and feeling of use.

As the blending amount of the gelling agent, depending on the kind of the gelling agent or the like, in general, 0.3 to 15.0% by weight relative to the total amount of the viscous substance (Y) is preferable, more preferably 0.3 to 8.0% by weight, still more preferably 1.5 to 5.0 wt%. If the content is less than 0.3% by weight, the amount of the granular material (X) relative to the viscous material (Y), the blending component of the granular material (X), the blending ratio and the like will depend on the viscosity (Y). This is because the gelation is insufficient and the generated carbon dioxide may bubble or disperse in the atmosphere. On the contrary, when it exceeds 15.0 weight%, it depends also on the usage-amount of the granular material (X) with respect to a viscous material (Y), the compounding component of a granular material (X), a compounding ratio, etc. It is because there is a possibility that the viscosity of) becomes too high, so that further dissolution of the granular material (X) becomes difficult, and the reaction between the weak acid and calcium carbonate is unlikely to occur.

As the calcium ion scavenger constituting the viscous substance (Y), an alkali or neutral one can be used while binding calcium ions competitively with the gelling agent. In the first composition for preparing carbon dioxide external gel, the particulate matter (A) contains a calcium ion scavenger, so even if it is acidic, it does not generate carbon dioxide by reacting with calcium carbonate during storage. However, in this embodiment, since a calcium ion trapping agent is included in the viscous substance (Y), carbonic acid will generate | occur | produce by reacting with calcium carbonate in preparation of the viscous substance (Y) if it is acidic. For this reason, in this embodiment, a calcium ion trapping agent not only binds a calcium ion competitively with a gelling agent, but also uses an alkaline or neutral thing. For example, sodium hexametaphosphate, tetrasodium pyrophosphate, disodium hydrogen phosphate, trisodium citrate, sodium polycarboxylic acid, sodium hydroxyethylidene diphosphonate, trisodium ethylenediamine tetraacetate, sodium ethylenediamine tetraacetate, Sodium hydroxyethyl ethylenediamine triacetate, diethylenetriamine pentaacetate, sodium ethylenediamine tetraacetate, and the like. You may use these individually or in combination of 2 or more types. Preferable examples include disodium hydrogen phosphate.

And as a compounding quantity of a calcium ion trapping agent, although it depends also on the kind of calcium ion trapping agent, etc., 0.1-1.0 weight% is preferable normally with respect to whole viscosity (Y) whole quantity. If less than 0.1% by weight, depending on the amount of the granular material (X) to the viscous material (Y), the blending component of the granular material (X), the blending ratio, and the like, the calcium ions are insufficiently captured and gelation and gel curing are rapid. This is because there is a concern that the generation of carbon dioxide may stop. On the contrary, when it exceeds 1.0 weight%, it depends also on the compounding component, compounding ratio of granular material (X) with respect to viscous material (Y), and the usage-amount of granular material (X), etc., but it catches too much calcium ion and gelatinizes and hardens | cures a gel sufficiently. This is because the generated carbon dioxide may bubble in the gel or disperse in the atmosphere.

As water constituting the viscous substance (Y), natural water, tap water, distilled water, purified water and the like are used without particular limitation. The reason why water is an essential component is the same reason as that of the first composition for preparing carbon dioxide external gel.

And as a compounding quantity of water, although it depends also on the kind of other raw materials, compounding quantity, etc., 70-95 weight% is preferable normally with respect to viscous substance (Y) whole quantity. It is because when it is less than 70 weight%, granular material X will melt | dissolve easily and it will become difficult to react reaction of weak acid and calcium carbonate. On the contrary, when it exceeds 95 weight%, since the compounding quantity of another essential component is too small, when granular material (X) is mixed, gelation and hardening of a gel may become inadequate or the generation amount of carbon dioxide may become inadequate.

When the viscous substance (Y) containing calcium carbonate, a gelling agent, a calcium ion trapping agent, and water as essential components is mixed with the granular substance (X), the granular substance (X) can be spread evenly and can be easily uniformly dispersed. It is preferable to have a viscosity of the degree. In addition, when the particulate matter (X) and the viscous material (Y) are mixed and then directly applied to the skin mucosa and used, it is preferable to have a viscosity such that it does not flow down from the skin mucosa immediately after mixing. .

A viscous substance (Y) can be manufactured by adding and mixing to the said essential component the adhesive etc. for improving affinity with the skin mucosal surface as needed. The kind, compounding quantity, etc. of an adhesive are the same as the composition for 1st carbon dioxide external gel preparation.

The 2nd carbon dioxide external gel preparation composition which consists of the said granular material (X) and viscous material (Y) can be used as follows, for example. That is, first, the granular material X and the viscous material Y are mixed at various ratios in various containers. Both ratios are preferably set such that calcium carbonate reacts with both weak acids. However, the reaction between calcium carbonate and the weak acid is so fast that the gelation and curing of the gel proceed rapidly, or the carbon dioxide is generated so fast that the carbon dioxide bubbles in the gel or disperses in the atmosphere. It is not preferable to use much for the viscous substance (Y). More specifically, the molar ratio of the weak acid of the particulate matter (X) and the calcium carbonate of the viscous substance (Y) is preferably 0.4 to 40 in the case of 0.1% by weight of calcium carbonate, and 0.3% by weight of calcium carbonate In the case of blending, about 0.04-3.6 is preferable, and in the case of blending 6.0 wt% of calcium carbonate, about 0.02-0.54 is preferable. Immediately thereafter, the obtained mixture is applied to a predetermined portion of the skin mucosa. At this time, a carbon dioxide external gel in which carbon dioxide generated by the reaction of weak acid and calcium carbonate is dissolved in the gel in a substantially non-bubble state is obtained, and the carbon dioxide is absorbed into the transmucosal mucosa of the skin mucosa, thereby obtaining a strong cosmetic or medical effect. . In addition, when the mixing ratio of the raw material is adjusted, the gel hardens when a certain time elapses after preparation, so that the gel can be easily removed from the skin mucosa.

Moreover, the raw material normally used for external preparations or cosmetics, for example a fragrance | flavor, a pigment, surfactant, an oil, and a humectant, in the range which does not impair the effect of this invention to at least one of granular substance (X) and viscous substance (Y). , Thickeners, alcohols, preservatives, antioxidants, colorants, ultraviolet absorbers and scattering agents, drugs and the like may be blended as necessary. Thereby, the carbon dioxide external gel obtained can be used suitably as an external medicine and cosmetics. Especially, it is preferable to use alcohol with respect to a viscous substance (Y) for the reason that the usability improves that the spreadability of a gel improves. Moreover, in order to improve the viscosity and adhesiveness of a gel, it is preferable to use a thickener with respect to at least one of a granular material (X) and a viscous material (Y). As alcohols and thickeners, the same ones as those of the first composition for preparing carbon dioxide external gel can be used.

Moreover, in the composition for carbon dioxide external gel preparation according to the present embodiment, the granular material (X) and the viscous material (Y) may be stored in a substantially non-contacting state until use, and are preferably stored in a closed state. . The storage container can be used without any particular limitations such as material, shape and structure. For example, the material may be plastic, glass, aluminum, paper, various polymers or composites of these materials. A cup, a tube, a bag, a bottle, a stick, a pump, etc. are mentioned, Any one of these can be used without a restriction | limiting in particular.

Next, the carbon dioxide external gel preparation composition of the present invention will be described in detail with reference to Examples, but the present invention is not limited to these Examples. In addition, in the following description, "part by weight" is abbreviated as "part."

First, Examples 1 to 5 below are examples of the first composition for preparing carbon dioxide external gel.

Example 1

(Preparation of granular material (A))

57 parts of sodium dihydrogen phosphate as a weak acid and 43 parts of ethylenediamine tetraacetate as calcium trapping agents were used, and granular granules (average particle size 0.3mm) were prepared with an appropriate amount of water.

(Preparation of Viscosity (B))

1 part of calcium carbonate, 3.5 parts of sodium alginate as gelling agent gelling with calcium ions, 87.9 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as adhesive to enhance affinity with the mucosal surface, 1,3 as alcohol A viscous substance (B) was prepared using 3.5 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 2

(Preparation of granular material (A))

53 parts of sodium dihydrogen phosphate as a weak acid, 6 parts of disodium ethylenediamine tetraacetate as a calcium scavenger, 36 parts of lactose as a dispersing agent, and 5 parts of dextrin as a binder are used, and granular granules (average particle diameter: 0.2 mm) are prepared with an appropriate amount of water. did.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 86 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as an adhesive to enhance affinity with the mucous membrane surface, 1,3 as alcohols A viscous substance (B) was prepared using 6 parts of butylene glycol, 0.5 parts of phenoxyethanol as an antiseptic, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 3

(Preparation of granular material (A))

56 parts of sodium dihydrogen phosphate as a weak acid, 6 parts of disodium ethylenediamine tetraacetate as a calcium scavenger, 33 parts of lactose as a dispersant, and 5 parts of dextrin as a binder were used to prepare granular granules (average particle size 0.3 mm) with an appropriate amount of water. did.

(Preparation of Viscosity (B))

0.3 parts of calcium carbonate, 3.5 parts of sodium alginate as gelling agent gelling with calcium ions, 85.1 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as adhesive to increase affinity with the mucous membrane surface, 1,3 as alcohol A viscous substance (B) was prepared by using 7 parts of butylene glycol, 0.5 parts of phenoxyethanol as an antiseptic, and 2.7 parts of pentylene glycol as an alcohol and an antiseptic.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 4

(Preparation of granular material (A))

65 parts of sodium dihydrogen phosphate as a weak acid and 35 parts of ethylenediamine tetraacetates as a calcium trapping agent were used, and granular granular material (average particle diameter 0.3mm) was prepared with the appropriate amount of water.

(Preparation of Viscosity (B))

1.0 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 87.9 parts of purified water as water, 3.5 parts of 1,3-butylene glycol as alcohols, as an adhesive for enhancing affinity with the mucosal surface A viscous substance (B) was prepared using 0.9 parts of sodium carboxymethylcellulose, 0.5 parts of phenoxyethanol as an antiseptic, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 5

(Preparation of granular material (A))

60 parts of sodium dihydrogen phosphate, 5 parts of potassium dihydrogen phosphate, and 35 parts of ethylenediamine diacetate acetate as calcium scavenger were used as a weak acid, and the granular granule (average particle diameter 0.2mm) was prepared with the appropriate amount of water.

(Preparation of Viscosity (B))

1.0 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 87.9 parts of purified water as water, 3.5 parts of 1,3-butylene glycol as alcohols, as an adhesive for enhancing affinity with the mucosal surface A viscous substance (B) was prepared using 0.9 parts of sodium carboxymethylcellulose, 0.5 parts of phenoxyethanol as an antiseptic, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Examples 6 to 25 below use sodium dihydrogen phosphate as a weak acid of the particulate matter (A) as an example of the first composition for preparing carbon dioxide external gel, and as a calcium ion capturing agent of the particulate matter (A). It is an example in which ethylenediamine disodium tetraacetate is used and the compounding ratio of both is mainly changed.

Example 6

(Preparation of granular material (A))

23.1 parts of sodium dihydrogen phosphate as a weak acid, 3.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 68.9 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

0.3 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 85.1 parts of purified water as water, 0.9 parts of sodium carboxymethylcellulose as an adhesive for enhancing affinity with the mucosal surface, 1, as alcohols A viscous substance (B) was prepared using 7.0 parts of 3-butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 7

(Preparation of granular material (A))

30.8 parts of sodium dihydrogen phosphate as a weak acid, 5.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 59.2 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 6, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 8

(Preparation of granular material (A))

43.1 parts of sodium dihydrogen phosphate as weak acid, 6.0 parts of disodium ethylenediamine tetraacetate as calcium ion scavenger, 5.0 parts of dextrin as binder, 45.9 parts of lactose as dispersant, and granular granular product (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 6, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 9

(Preparation of granular material (A))

53.8 parts of sodium dihydrogen phosphate as a weak acid, 10.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 31.2 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 6, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 10

(Preparation of granular material (A))

5.4 parts of sodium dihydrogen phosphate as a weak acid, 0.5 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 89.1 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 85.0 parts of purified water as water, 0.9 parts of sodium carboxymethylcellulose as an adhesive for enhancing affinity with the mucosal surface, 1, as alcohols A viscous substance (B) was prepared using 7.0 parts of 3-butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 11

(Preparation of granular material (A))

5.4 parts of sodium dihydrogen phosphate as a weak acid, 0.84 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 88.76 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 10, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 12

(Preparation of granular material (A))

9.6 parts of sodium dihydrogen phosphate as weak acid, 1.5 parts of disodium ethylenediamine tetraacetate as calcium ion scavenger, 5.0 parts of dextrin as binder, 83.9 parts of lactose as dispersant, granular granule (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 10, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 13

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 4.2 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 52.3 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 10, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 14

(Preparation of granular material (A))

23.1 parts of sodium dihydrogen phosphate as a weak acid and 5.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent were used, and granular granules (average particle diameter 0.3mm) were prepared with the appropriate amount of 50% ethanol.

(Preparation of Viscosity (B))

In the same manner as in Example 10, a viscous substance (B) was prepared.

And the obtained granular material (A) and viscous material (B) were combined, and it was set as the composition for carbon dioxide external gel preparation.

Example 15

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 50.5 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 10, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 16

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 10.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 46.5 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 10, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 17

(Preparation of granular material (A))

40.8 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 48.2 parts of lactose as a dispersing agent, and the granular granule (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 10, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 18

(Preparation of granular material (A))

65.4 parts of sodium dihydrogen phosphate as a weak acid, 10.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 19.6 parts of lactose as a dispersing agent, and a granular granular product with an appropriate amount of 50% ethanol (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 10, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 19

(Preparation of granular material (A))

30.8 parts of sodium dihydrogen phosphate as a weak acid, 8.0 parts of sodium diacetate acetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 56.2 parts of lactose as a dispersing agent, and granular granules (average particle diameter) 0.3 mm) was prepared.

(Preparation of Viscosity (B))

0.5 parts of calcium carbonate, 3.5 parts of sodium alginate as gelling agent gelling with calcium ions, 84.9 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as adhesive to increase affinity with the mucous membrane surface, 1,3 as alcohol A viscous substance (B) was prepared using 7.0 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 20

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 12 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 44.5 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 19, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 21

(Preparation of granular material (A))

53.8 parts of sodium dihydrogen phosphate as a weak acid, 10.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 31.2 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 19, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 22

(Preparation of granular material (A))

43.8 parts of sodium dihydrogen phosphate as a weak acid, 43.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, and 13.2 parts of lactose as a dispersing agent were used, and granular granules (average particle diameter 0.3mm) were prepared with the appropriate amount of 50% ethanol.

(Preparation of Viscosity (B))

1.0 part of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 87.9 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as an adhesive to enhance affinity with the mucosal surface, 1,3 as alcohols A viscous substance (B) was prepared using 3.5 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the obtained granular material (A) and viscous material (B) were combined, and it was set as the composition for carbon dioxide external gel preparation.

Example 23

(Preparation of granular material (A))

46.2 parts of sodium dihydrogen phosphate as a weak acid, 8.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 40.8 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 22, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 24

(Preparation of granular material (A))

48.5 parts of sodium dihydrogen phosphate as a weak acid, 37.0 parts of disodium ethylenediamine tetraacetate as a calcium ion trapping agent, and 14.5 parts of lactose as a dispersing agent were used, and granular granules (average particle size 0.3mm) were prepared with the appropriate amount of 50% ethanol.

(Preparation of Viscosity (B))

In the same manner as in Example 22, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 25

(Preparation of granular material (A))

50.0 parts of sodium dihydrogen phosphate as a weak acid, 35.0 parts of disodium ethylenediamine tetraacetate as a calcium ion trapping agent, and 15.0 parts of lactose as a dispersing agent were used, and granular granules (average particle diameter 0.3mm) were prepared with the appropriate amount of 50% ethanol.

(Preparation of Viscosity (B))

In the same manner as in Example 22, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Examples 26 to 36 below use sodium dihydrogen phosphate or potassium dihydrogen phosphate as the weak acid of the granular material (A) as an example of the first composition for preparing carbon dioxide external gel. Glycine is used as a calcium ion trapping agent, and the compounding ratio of both is mainly changed.

Example 26

(Preparation of granular material (A))

5.4 parts of sodium dihydrogen phosphate as a weak acid, 3.0 parts of glycine as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 86.6 parts of lactose as a dispersing agent, the granular granule (average particle diameter 0.3mm) was prepared with the appropriate amount of 50% ethanol. did.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 85.0 parts of purified water as water, 0.9 parts of sodium carboxymethylcellulose as an adhesive for enhancing affinity with the mucosal surface, 1, as alcohols A viscous substance (B) was prepared using 7.0 parts of 3-butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 27

(Preparation of granular material (A))

5.4 parts of sodium dihydrogen phosphate as a weak acid, 5.6 parts of glycine as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 84.0 parts of lactose as a dispersing agent, the granular granule (average particle diameter 0.3mm) was prepared with the appropriate amount of 50% ethanol. did.

(Preparation of Viscosity (B))

In the same manner as in Example 26, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 28

(Preparation of granular material (A))

9.6 parts of potassium dihydrogen phosphate as a weak acid, 10.0 parts of glycine as a calcium ion scavenger, 5.0 parts of dextrin as a binder, 75.4 parts of lactose as a dispersant were prepared, and granular granules (average particle size 0.3 mm) were prepared with an appropriate amount of 50% ethanol. did.

(Preparation of Viscosity (B))

In the same manner as in Example 26, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 29

(Preparation of granular material (A))

28.5 parts of potassium dihydrogen phosphate as a weak acid, 21.2 parts of glycine as a calcium ion scavenger, 5.0 parts of dextrin as a binder, and 45.3 parts of lactose as a dispersant were prepared, and granular granules (average particle size 0.3 mm) were prepared with an appropriate amount of 50% ethanol. did.

(Preparation of Viscosity (B))

In the same manner as in Example 26, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 30

(Preparation of granular material (A))

28.5 parts of sodium dihydrogen phosphate as a weak acid, 30.0 parts of glycine as a calcium ion trapping agent, 10.0 parts of dextrin as a binder, and 31.5 parts of lactose as a dispersing agent were used, and granular granules (average particle size 0.3 mm) were prepared with an appropriate amount of 50% ethanol. did.

(Preparation of Viscosity (B))

In the same manner as in Example 26, a viscous substance (B) was prepared.

And the obtained granular material (A) and viscous material (B) were combined, and it was set as the composition for carbon dioxide external gel preparation.

Example 31

(Preparation of granular material (A))

28.5 parts of sodium dihydrogen phosphate as a weak acid, 49.4 parts of glycine as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 82.9 parts of lactose as a dispersing agent were used, and granular granules (average particle size 0.3 mm) were prepared with an appropriate amount of 50% ethanol. did.

(Preparation of Viscosity (B))

In the same manner as in Example 26, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 32

(Preparation of granular material (A))

37.7 parts of sodium dihydrogen phosphate as a weak acid, 49.0 parts of glycine as a calcium ion trapping agent, and 2.0 parts of dextrin as binders were used, and granular granules (average particle diameter 0.3mm) were prepared with the appropriate amount of 50% ethanol.

(Preparation of Viscosity (B))

In the same manner as in Example 26, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 33

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 12.0 parts of glycine as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, and 44.5 parts of lactose as a dispersing agent were used, and granular granules (average particle size 0.3 mm) were prepared with an appropriate amount of 50% ethanol. did.

(Preparation of Viscosity (B))

In the same manner as in Example 26, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 34

(Preparation of granular material (A))

40.5 parts of sodium dihydrogen phosphate as a weak acid and 42.3 parts of glycine as a calcium ion trapping agent were used, and granular granules (average particle diameter 0.3mm) were prepared with the appropriate amount of 50% ethanol.

(Preparation of Viscosity (B))

In the same manner as in Example 26, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 35

(Preparation of granular material (A))

65.4 parts of sodium dihydrogen phosphate as a weak acid and 15.0 parts of glycine as a calcium ion trapping agent were used, and granular granules (average particle size 0.3mm) were prepared with the appropriate amount of 50% ethanol.

(Preparation of Viscosity (B))

In the same manner as in Example 26, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 36

(Preparation of granular material (A))

74.6 parts of sodium dihydrogen phosphate as a weak acid and 3.0 parts of glycine as calcium ion trapping agents were used, and granular granules (average particle size 0.3mm) were prepared with the appropriate amount of 50% ethanol.

(Preparation of Viscosity (B))

In the same manner as in Example 26, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Examples 37 to 40 below use phosphoric acid as a weak acid of particulate matter (X), using disodium hydrogen phosphate as the calcium ion capturing agent of the viscous substance (Y) as an example of the second composition for preparing carbon dioxide external gel. Sodium dihydrogen phosphate is used, and the compounding ratio of this sodium dihydrogen phosphate is variously changed.

Example 37

(Preparation of granular material (X))

26.9 parts of sodium dihydrogen phosphate as a weak acid, 5.0 parts of dextrin as a binder, and 68.1 parts of lactose as a dispersing agent were used, and granular granules (average particle size 0.3mm) were prepared with the appropriate amount of 50% ethanol.

(Preparation of Viscosity (Y))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 0.7 parts of disodium hydrogen phosphate dihydrate as calcium ion scavenger, 84.3 parts of purified water as water, as an adhesive for enhancing affinity with the mucosal surface Viscosity (Y) was prepared by using 0.9 parts of carboxymethylcellulose sodium, 7.0 parts of 1,3-butylene glycol as alcohols, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the obtained granular material (X) and viscous material (Y) were combined, and it was set as the composition for carbon dioxide external gel preparation.

Example 38

(Preparation of granular material (X))

34.6 parts of sodium dihydrogen phosphate as a weak acid, 5.0 parts of dextrin as a binder, and 60.4 parts of lactose as a dispersing agent were used, and granular granules (average particle size 0.3mm) were prepared with the appropriate amount of 50% ethanol.

(Preparation of Viscosity (Y))

In the same manner as in Example 37, a viscous substance (Y) was prepared.

And the obtained granular material (X) and viscous material (Y) were combined, and it was set as the composition for carbon dioxide external gel preparation.

Example 39

(Preparation of granular material (X))

42.3 parts of sodium dihydrogen phosphate as a weak acid, 5.0 parts of dextrin as a binder, and 52.7 parts of lactose as a dispersing agent were used, and granular granules (average particle size 0.3mm) were prepared with the appropriate amount of 50% ethanol.

(Preparation of Viscosity (Y))

In the same manner as in Example 37, a viscous substance (Y) was prepared.

And the obtained granular material (X) and viscous material (Y) were combined, and it was set as the composition for carbon dioxide external gel preparation.

Example 40

(Preparation of granular material (X))

50.0 parts of sodium dihydrogen phosphate as a weak acid, 5.0 parts of dextrins as a binder, and 45.0 parts of lactose as a dispersing agent were used, and granular granules (average particle size 0.3mm) were prepared with the appropriate amount of 50% ethanol.

(Preparation of Viscosity (Y))

In the same manner as in Example 37, a viscous substance (Y) was prepared.

And the obtained granular material (X) and viscous material (Y) were combined, and it was set as the composition for carbon dioxide external gel preparation.

Examples 41 to 59 described below are examples of the first composition for preparing carbon dioxide external gel, wherein the granular material (A) contains a binder, and the type and compounding ratio of the binder are variously changed.

Example 41

(Preparation of granular material (A))

40.8 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 10.0 parts of potato starch as a binder, 38.2 parts of lactose as a dispersant, and granulated with an appropriate amount of 50% ethanol. The granular material (average particle diameter 0.3mm) of the phase was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 85.0 parts of purified water as water, 0.9 parts of sodium carboxymethylcellulose as an adhesive to enhance affinity with the mucosal surface, 1,3 as alcohols A viscous substance (B) was prepared using 7.0 parts of butylene glycol and 0.5 parts of phenoxyethanol, alcohols and 2.7 parts of pentylene glycol as preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 42

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 10.0 parts of potato starch as a binder, 40.5 parts of lactose as a dispersant, and granulated with an appropriate amount of 50% ethanol The granular material (average particle diameter 0.3mm) of the phase was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 43

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of sodium carboxymethylcellulose as a binder, 50.5 parts of lactose as a dispersing agent, and a granular granular material with an appropriate amount of 50% ethanol ( An average particle diameter of 0.3 mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 44

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of methylcellulose as a binder, 50.5 parts of lactose as a dispersing agent, and the granular substance (average particle diameter) by 50% ethanol of appropriate amount 0.3 mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 45

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of hydroxypropyl starch as a binder, 50.5 parts of lactose as a dispersing agent, and a granular granular material with an appropriate amount of 50% ethanol ( An average particle diameter of 0.3 mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 46

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 5.0 parts of hydroxypropyl starch, and 45.5 parts of lactose as a dispersant, granulated with an appropriate amount of 50% ethanol The granular material (average particle diameter 0.3mm) of the phase was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 47

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as weak acid, 6.0 parts of disodium ethylenediamine tetraacetate as calcium ion scavenger, 5.0 parts of potato starch as binder, 50.5 parts of lactose as dispersant, and granular granules (average particle size) 0.3 mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 48

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of hydroxypropyl cellulose as a binder, 50.5 parts of lactose as a dispersing agent, and a granular granular material with an appropriate amount of 50% ethanol ( An average particle diameter of 0.3 mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the obtained granular material (A) and viscous material (B) were combined, and it was set as the composition for carbon dioxide external gel preparation.

Example 49

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as calcium ion scavenger, 5.0 parts of hydroxypropyl cellulose as binder, 10.0 parts of potato starch, 40.5 parts of lactose as dispersant, Granular granules (average particle diameter: 0.3 mm) were prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 50

(Preparation of granular material (A))

50.0 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of hydroxypropyl cellulose as a binder, 39.0 parts of lactose as a dispersing agent, and a granular granular material with an appropriate amount of 50% ethanol ( An average particle diameter of 0.3 mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the obtained granular material (A) and viscous material (B) were combined, and it was set as the composition for carbon dioxide external gel preparation.

Example 51

(Preparation of granular material (A))

50.0 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of hydroxypropyl cellulose as a binder, 39.0 parts of lactose as a dispersing agent, and a granular granular material with an appropriate amount of 50% ethanol ( An average particle diameter of 0.3 mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 52

(Preparation of granular material (A))

50.0 parts of sodium dihydrogen phosphate as weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as calcium ion trapping agent, 5.0 parts of hydroxypropyl cellulose as binder, 10.0 parts of potato starch, 29.0 parts of lactose as dispersant, Granular granules (average particle diameter: 0.3 mm) were prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the obtained granular material (A) and viscous material (B) were combined, and it was set as the composition for carbon dioxide external gel preparation.

Example 53

(Preparation of granular material (A))

50.0 parts of sodium dihydrogen phosphate as weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of hydroxypropylmethylcellulose as a binder, 39.0 parts of lactose as a dispersing agent, and a granular granular material with an appropriate amount of 50% ethanol (Average particle diameter 0.3mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 54

(Preparation of granular material (A))

50.0 parts of sodium dihydrogen phosphate as weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of hydroxypropylmethylcellulose as a binder, 39.0 parts of lactose as a dispersing agent, and a granular granular material with an appropriate amount of 50% ethanol (Average particle diameter 0.3mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the obtained granular material (A) and viscous material (B) were combined, and it was set as the composition for carbon dioxide external gel preparation.

Example 55

(Preparation of granular material (A))

50.0 parts of sodium dihydrogen phosphate as weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of hydroxypropylmethylcellulose as a binder, 39.0 parts of lactose as a dispersing agent, and a granular granular material with an appropriate amount of 50% ethanol (Average particle diameter 0.3mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 56

(Preparation of granular material (A))

50.0 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 10.0 parts of dextrin as a binder, 34.0 parts of lactose as a dispersing agent, and the granular granule (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 57

(Preparation of granular material (A))

50.0 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 10.0 parts of dextrin as a binder, 5.0 parts of low-substituted hydroxypropyl cellulose, 29.0 parts of lactose as a dispersing agent, Granular granules (average particle size 0.3 mm) were prepared with 50% ethanol.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 58

(Preparation of granular material (A))

50.0 parts of sodium dihydrogen phosphate as weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as calcium ion trapping agent, 10.0 parts of dextrin as binder, 2.0 parts of low-substituted hydroxypropyl cellulose, 32.0 parts of lactose as dispersant, 50% Granular granules (average particle size 0.3 mm) were prepared with ethanol.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 59

(Preparation of granular material (A))

50.0 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 10.0 parts of dextrin as a binder, 5.0 parts of crystalline cellulose, 29.0 parts of lactose as a dispersing agent, and granular granular form with 50% ethanol in an appropriate amount. Water (average particle diameter 0.3 mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 41, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Examples 60 to 69 below are examples of the first composition for preparing carbon dioxide external gel for dispersing, wherein the granular material (A) contains a dispersant and variously changed the type of the dispersant.

Example 60

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 10.0 parts of dextrin as a binder, 45.5 parts of lactose as a dispersing agent, and a granular granular product (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 85.0 parts of purified water as water, 0.9 parts of sodium carboxymethylcellulose as an adhesive to enhance affinity with the mucosal surface, 1,3 as alcohols A viscous substance (B) was prepared using 7.0 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 61

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 10.0 parts of dextrin as a binder, 45.5 parts of glucose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 60, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 62

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 10.0 parts of dextrin as a binder, 45.5 parts of sucrose as a dispersing agent, and a granular granular product (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 60, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 63

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 10.0 parts of dextrin as a binder, 45.5 parts of xylitol as a dispersing agent, and the granular material (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 60, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 64

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 10.0 parts of dextrin as a binder, and 45.5 parts of sorbitol as a dispersing agent, and the granular material (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 60, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 65

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as weak acid, 6.0 parts of disodium ethylenediamine tetraacetate as calcium ion trapping agent, 10.0 parts of dextrin as binder, 45.5 parts of mancitol as dispersant, and granular granules with appropriate amount of 50% ethanol (Average particle diameter 0.3mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 60, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 66

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 10.0 parts of dextrin as a binder, and 45.5 parts of mannitol as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 60, a viscous substance (B) was prepared.

And the obtained granular material (A) and viscous material (B) were combined, and it was set as the composition for carbon dioxide external gel preparation.

Example 67

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 10.0 parts of dextrin as a binder, 45.5 parts of urea as a dispersing agent, and a granular granular material (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 60, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 68

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as weak acid, 6.0 parts of disodium ethylenediamine tetraacetate as calcium ion scavenger, 10.0 parts of dextrin as binder, 45.5 parts of xanthan gum as dispersant, and granular granules (average particle size) 0.3 mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 60, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 69

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 10.0 parts of dextrin as a binder, 45.5 parts of pullulan as a dispersing agent, and a granular granular product (average particle diameter) 0.3 mm) was prepared.

(Preparation of Viscosity (B))

In the same manner as in Example 60, a viscous substance (B) was prepared.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Examples 70 to 86 below are examples of the first composition for preparing the carbon dioxide external gel, in which the viscous substance (B) contains a pressure-sensitive adhesive for increasing affinity with the skin mucosa and the like, and this viscous substance (B ) Is an example of various modifications of the formulation.

Example 70

(Preparation of granular material (A))

53.0 parts of sodium dihydrogen phosphate as a weak acid, 6.0 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 34.0 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 79.0 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as an adhesive to enhance affinity with the mucous membrane surface, 1,3 as alcohols A viscous substance (B) was prepared using 10.0 parts of butylene glycol, 0.5 part of phenoxyethanol as an antiseptic, and 5.7 parts of pentylene glycol as alcohols and an antiseptic.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 71

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as gelling agent gelling with calcium ions, 82.0 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as adhesive to increase affinity with the mucous membrane surface, 1,3 as alcohol A viscous substance (B) was prepared using 10.0 parts of butylene glycol, 0.5 parts of phenoxyethanol as an antiseptic, and 2.7 parts of pentylene glycol as alcohols and an antiseptic.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 72

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 84.7 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as an adhesive to enhance affinity with the mucosal surface, 1,3 as alcohols A viscous substance (B) was prepared using 10.0 parts of butylene glycol and 0.5 part of phenoxyethanol as an antiseptic.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 73

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as gelling agent gelling with calcium ions, 82.0 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as adhesive to increase affinity with the mucous membrane surface, 1,3 as alcohol A viscous substance (B) was prepared using 7.0 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 5.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 74

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as gelling agent gelling with calcium ions, 84.4 parts of purified water as water, 7.0 parts of 1,3-butylene glycol as alcohol, 0.5 part of phenoxyethanol as antiseptic, alcohols and preservatives As 2.7 parts of pentylene glycol were used as a viscous substance (B).

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 75

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 4.0 parts of sodium alginate as a gelling agent gelling with calcium ions, 84.9 parts of purified water as water, 0.5 parts of carboxymethylcellulose sodium as an adhesive to enhance affinity with the mucous membrane surface, 1,3 as alcohols A viscous substance (B) was prepared using 7.0 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 76

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 84.4 parts of purified water as water, 1.5 parts of sodium carboxymethylcellulose as an adhesive to enhance affinity with the mucous membrane surface, 1,3 as alcohols A viscous substance (B) was prepared using 7.0 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 77

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 86.0 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as an adhesive to enhance affinity with the mucous membrane surface, 1,3 as alcohols A viscous substance (B) was prepared using 6.0 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 78

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 2.9 parts of sodium alginate as a gelling agent gelling with calcium ions, 85.0 parts of purified water as water, 1.5 parts of sodium carboxymethylcellulose as an adhesive to enhance affinity with the mucosal surface, 1,3 as alcohols A viscous substance (B) was prepared using 7.0 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 79

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 1.9 parts of sodium alginate as a gelling agent gelling with calcium ions, 85.0 parts of purified water as water, 2.5 parts of sodium carboxymethylcellulose as an adhesive to enhance affinity with the mucous membrane surface, 1,3 as alcohols A viscous substance (B) was prepared using 7.0 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the obtained granular material (A) and viscous material (B) were combined, and it was set as the composition for carbon dioxide external gel preparation.

Example 80

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 0.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 85.0 parts of purified water as water, 3.9 parts of sodium carboxymethylcellulose as an adhesive to enhance affinity with the mucous membrane surface, 1,3 as alcohols A viscous substance (B) was prepared using 7.0 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 81

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as gelling agent gelling with calcium ions, 88.7 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as adhesive to enhance affinity with the mucous membrane surface, 1,3 as alcohols A viscous substance (B) was prepared using 6.0 parts of butylene glycol and 0.5 part of phenoxyethanol as an antiseptic.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 82

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as gelling agent gelling with calcium ions, 88.0 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as adhesive to enhance affinity with the mucosal surface, 1,3 as alcohol A viscous substance (B) was prepared using 4.0 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 83

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 89.0 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as an adhesive to enhance affinity with the mucosal surface, and phenoxyethanol 0.5 as antiseptic. Viscosity (B) was prepared using 5.7 parts of pentylene glycol as a part, alcohols, and an antiseptic.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 84

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 92.0 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as an adhesive to enhance affinity with the mucosal surface, and phenoxyethanol 0.5 as antiseptic. A viscous substance (B) was prepared using 2.7 parts of pentylene glycol as a part, alcohols, and an antiseptic.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 85

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.4 parts of calcium carbonate, 3.5 parts of sodium alginate as a gelling agent gelling with calcium ions, 94.7 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as an adhesive for enhancing affinity with the mucosal surface, and phenoxyethanol 0.5 as antiseptic. A viscous substance (B) was prepared using wealth.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 86

(Preparation of granular material (A))

In the same manner as in Example 70, a granular material (A) was prepared.

(Preparation of Viscosity (B))

0.3 parts of calcium carbonate, 3.5 parts of sodium alginate as gelling agent gelling with calcium ions, 85.1 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as adhesive to increase affinity with the mucous membrane surface, 1,3 as alcohol A viscous substance (B) was prepared using 7.0 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 87

(Preparation of granular material (A))

5.4 parts of sodium dihydrogen phosphate as a weak acid, 0.5 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 89.1 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

6.0 parts of calcium carbonate, 3.5 parts of sodium alginate as gelling agent gelling with calcium ions, 79.4 parts of purified water as water, 0.9 parts of carboxymethylcellulose sodium as adhesive to increase affinity with the mucosal surface, 1,3 as alcohol A viscous substance (B) was prepared using 7.0 parts of butylene glycol, 0.5 parts of phenoxyethanol as preservatives, and 2.7 parts of pentylene glycol as alcohols and preservatives.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Example 88

(Preparation of granular material (A))

38.5 parts of sodium dihydrogen phosphate as a weak acid, 4.2 parts of sodium ethylenediamine tetraacetate as a calcium ion trapping agent, 5.0 parts of dextrin as a binder, 52.3 parts of lactose as a dispersing agent, and granular granules (average particle size 0.3) mm) was prepared.

(Preparation of Viscosity (B))

A viscous substance (B) was prepared using 2.7 parts of calcium carbonate, 14.6 parts of sodium alginate as a gelling agent gelling with calcium ion, and 82.7 parts of purified water as water.

And the granular material (A) and viscous material (B) which were obtained were combined and it was set as the composition for carbon dioxide external gel preparation.

Comparative Example 1

It produced according to Example 109 of Unexamined-Japanese-Patent No. 2000-319187 as follows.

(Production of granular material)

Using 25 parts of citric acid, 25 parts of ethyl cellulose, and 50 parts of croscarmellose sodium, porous cylindrical granules having a length of about 4 mm and a diameter of about 1 mm were prepared by wet extrusion granulation using water as a solvent.

(Preparation of Viscous Composition)

Dissolve 2.4 parts of sodium hydrogen carbonate in 89.6 parts of purified water, slowly warm to 60 ° C, add 4.0 parts of sodium alginate, 2.0 parts of ethyl cellulose, and 2.0 parts of carboxymethylcellulose sodium to dissolve while stirring. Manufactured.

And the obtained particulate matter and the viscous composition were combined and it was set as the composition for carbon dioxide external preparations.

Comparative Example 2

It produced according to Example 1 of WO02 / 080941 as follows.

(Production of granular material)

50 parts of lactose as a water-soluble dispersant, 30 parts of citric acid as a water-soluble acid, 7 parts of processed starch as a thickener, 3 parts of dextrin, and 10 parts of potato starch. Porous columnar granules were prepared.

(Preparation of Viscous Composition)

Dissolve 4.0 parts of sodium hydrogen carbonate as carbonate in 91.5 parts of purified water and slowly warm it up to 60 ° C while slowly adding 1.5 parts of sodium alginate and 3.0 parts of sodium carboxymethylcellulose as a thickener to dissolve with stirring, and then, after dissolution, leave it overnight to cool to room temperature to prepare a viscous composition. did.

And the granular material and the viscous composition were combined and it was set as the composition for carbon dioxide external preparation preparation of the comparative example 2.

Thus, the composition for carbon dioxide external gel preparation of the Example and the composition for carbon dioxide external preparation of the comparative example were evaluated as follows.

Evaluation 1: Partial slimming, whitening, and skin smoothing effects on the face

About the carbon dioxide external gel preparation composition of Examples 1-5, 1.2 g of granular material and 20 g of viscous materials were mixed 30 times using the plastic spatula, and the carbon dioxide external gel was prepared.

About the composition for carbon dioxide external preparation preparation of the comparative example 1, the granular material 2g and the viscous material 30g were mixed 30 times using the plastic spatula, and the carbon dioxide external preparation was prepared.

About the carbon dioxide external preparation preparation composition of the comparative example 2, the granular material 1.4g and the viscous composition 30g were mixed 30 times using the spatula in the plastic container, and the carbon dioxide external preparation was prepared.

In any of the compositions for preparing carbon dioxide external gels of Examples 1 to 5, mixing of the particulate matter and the viscous substance was easy. In any of the examples, the granules were dispersed evenly in the viscous substance, and substantially no bubble carbon dioxide appeared in the gel, and a flowable gel having moderate viscosity, adhesiveness, and flexibility was obtained.

When the obtained fluid gel was applied to the face of a female subject of 27 to 42 years old with a thickness of about 0.5 mm, all of them had sufficient fluidity, good spreadability, and were applied to the entire face with a uniform thickness and did not flow down at all. Immediately after application, all gels were very cold and persisted during application. In addition, since the carbon dioxide generation reaction by the reaction of acid and carbonate is an endothermic reaction, the sustained cooling of the gel indicates that the reaction continues. For all gels, the subject felt a sensation of tightening or diminishing face. After 15 minutes, the gel was removed, but all the gels obtained from the carbon dioxide external gel preparation compositions of Examples 1 to 5 were suitably cured to form a hydrogel sheet, and were easily peeled off from the face. In addition, in all gels, the subject became whiter and smoother in skin than before the gel was applied, and there was no clearness and dullness. In addition, the partial slimming effect of the ball becoming smaller and the lift up effect of raising the ball and the corner were shown in all the gels. Especially the gel obtained from the composition for carbon dioxide external gel preparation of Example 2 was excellent in usability, such as ease of application | coating or peeling off, and both sides of an effect. Moreover, when all the gels apply | coated for 30 minutes or more, a feeling of cooling continued and the said cosmetic effect was acquired.

On the other hand, the composition for preparing the carbon dioxide external preparation of Comparative Example 1 was easy to mix the particulate matter and the viscous composition, but many bubbles were contained in the obtained carbon dioxide external preparation, and the bubbles were destroyed when pressed with a spatula. As a result of applying the carbon dioxide external preparation to the subject's cheeks, it immediately flowed down immediately after application, thereby soiling the garment. In addition, a feeling of cold was immediately felt after application, but after about 3 minutes, the feeling of cold disappeared, indicating that there was no persistence in the carbon dioxide generating reaction. The carbon dioxide external preparation was removed 15 minutes after the application, but was very viscous and was not removed only by washing with water, but had to be washed with soap. Although the skin became somewhat white after removal, there was no partial slimming effect of the ball becoming smaller and a lift-up effect of raising the ball and corner angle.

In addition, although the carbon dioxide external gel obtained from the composition for preparing carbon dioxide external gel of the present invention was about 20 g or more to be applied to the entire face, the carbon dioxide external agent obtained from the carbon dioxide external agent preparation composition of Comparative Example 1 was about 30 g. Moreover, there was a feeling that it was somewhat insufficient to apply to the entire face so as not to destroy bubbles in the carbon dioxide external preparation.

In addition, in the composition for preparing a carbon dioxide external preparation of Comparative Example 2, mixing of the granular material and the viscous composition was easy, and all of the granular material was spread evenly in the viscous composition, and generation of carbon dioxide was sufficient. In addition, the obtained carbon dioxide external preparation did not flow even if it applied to the ball of a subject. However, after removing after 15 minutes, the subject's cheeks were observed. As a result, the whitening effect and the like were weaker than those of Examples 1 to 5. In addition, since the washing with water was required to completely remove the carbon dioxide external agent applied to the ball, there was a feeling that some subjects were somewhat troublesome.

 Rate 2: partial slimming, whitening, skin smoothing effect of the arm

4 g of the granular material (A) and 60 g of the viscous material (B) of the composition for preparing a carbon dioxide external gel preparation of Example 2 were mixed 30 times with a spatula to prepare a carbon dioxide external gel. All the granules were spread evenly in the viscous substance, and substantially no foamed carbon dioxide appeared in the gel, and a flowable gel having moderate viscosity, adhesiveness, and flexibility was obtained. The fluid gel was applied to the right upper arm of a 35-year-old woman, and as a result, fluidity was sufficient, spreadability was good, applied to a uniform thickness, and did not flow down at all. Immediately after application, the flowable gel was very cold and persisted during application. After 25 minutes, the gel was removed, and the gel was cured appropriately to form a hydrogel sheet, which was easily peeled off the upper arm. When the peripheral length of the upper arm was measured, it decreased 1 cm from 27.5 cm to 26.5 cm before gel application, and a partial slimming effect was observed. In addition, the coated part was clearly white and smooth compared to the surrounding skin.

Evaluation 3: treatment of wounds (1)

For a 1 cm × 3 cm abrasion of the left elbow of a 9 year old girl, a carbon dioxide external gel was prepared using 0.5 g of granular material (A) and 7 g of a viscous material (B) of the composition for preparing carbon dioxide external gel of Example 1, It applied for 30 minutes. Immediately after preparation, the gel was soft, had good spreadability, and was easy to apply. The feeling of cooling at the application site persisted during application and the pain and itching of the wound disappeared. When the gel was removed after 30 minutes, it was cured appropriately to form a hydrogel sheet and could be easily removed. This was repeated once a day for 5 days, and the wound was completely healed and healed without pigmentation.

Evaluation 4: Treatment of Contact Dermatitis

For contact dermatitis with 4 cm x 7 cm red color on the left side of the forehead of a 27-year-old woman, carbon dioxide externalization was carried out using 0.5 g of granular material (A) and 15 g of viscous material (B) of the composition for preparing carbon dioxide external gel of Example 4 The gel was prepared and applied for 20 minutes. Immediately after preparation, the gel was soft, had good spreadability, and was easy to apply. The feeling of cooling at the application site persisted during application, eliminating itch. After 20 minutes, the gel was removed, which was cured appropriately to form a hydrogel sheet, which was easily removed. After the gel was removed, the redness and blackness of contact dermatitis disappeared and healed.

Evaluation 5: reaction by generation and absorption of carbon dioxide

All of the following evaluations were performed on the 27-year-old female monitor.

A carbon dioxide external gel was prepared using 0.2 g of granular material (A) and 3.0 g of viscous material (B) of each of the carbon dioxide external gel preparation compositions of Examples 6 to 9, respectively, and the forearm part or the lower thigh part. ) Was applied. As a result, in all, reaction (evaporation of skin, a feeling of cold, etc.) by absorption of generated carbon dioxide occurred. The coated carbon dioxide external gel could be applied on the skin mucosa without hardening within 5 minutes after preparation. The surface was hardened in about 15 to 20 minutes, and after 30 minutes, a gel on a hydrogel sheet was formed. It was able to be peeled off cleanly, and very good result was obtained.

Carbon dioxide external gels were prepared using 0.3 g of granules (A) and 3.0 g of viscous materials (B) of the compositions for preparing carbon dioxide external gels of Examples 10 to 13 and 15 to 18, respectively, and applied to the forearm or lower thigh. As a result, in all, reaction (evaporation of skin, a feeling of cold, etc.) by absorption of generated carbon dioxide occurred. In addition, each of the carbon dioxide external gels obtained in Examples 10 and 11 was hardened within 30 minutes and hydrogel sheeted.

On the other hand, each of the carbon dioxide external gels obtained in Examples 12, 13, and 15 to 18 could be applied onto the skin mucosa without curing within 5 minutes after preparation, and the surface solidified in about 15 to 20 minutes, and after 30 minutes A gel on the hydrogel sheet was formed which was then able to be peeled off cleanly from the skin and very good results were obtained.

The carbon dioxide external gel was prepared using 0.15 g of the granular material (A) and 3.0 g of the viscous material (B) of the composition for preparing the carbon dioxide external gel of Example 14, and applied to the forearm or the lower thigh. As a result, a reaction (redness of the skin, feeling of cold, etc.) occurred due to absorption of the generated carbon dioxide. Moreover, the apply | coated carbon dioxide external gel hardened within 30 minutes, and was hydrogel-ized.

The carbon dioxide external gel was prepared using the granular material (A) 0.2g and the viscous material (B) 3.0g of each of the composition for preparing carbon dioxide external gel of Examples 19 to 25, respectively, and applied to the forearm or the lower thigh. As a result, in all, reaction (evaporation of skin, a feeling of cold, etc.) by absorption of generated carbon dioxide occurred. In addition, each of the carbon dioxide external gels obtained in Examples 21 to 25 was hardened within 30 minutes and hydrogel sheeted. On the other hand, each of the carbon dioxide external gels obtained in Examples 19 and 20 could be applied onto the skin mucosa without curing within 5 minutes after preparation, and the surface was hardened in about 15 to 20 minutes, and after 30 minutes, A gel was formed which could then be peeled off cleanly from the skin and very good results were obtained.

The carbon dioxide external gels were prepared using 0.3 g of granules (A) and 3.0 g of viscous materials (B) of the compositions for preparing carbon dioxide external gels of Examples 26 to 36, respectively, and applied to the forearm or lower thigh. As a result, in all, reaction (evaporation of skin, a feeling of cold, etc.) by absorption of generated carbon dioxide occurred. In addition, each applied carbon dioxide external gel could be applied onto the skin mucosa without hardening within 5 minutes of preparation, and the surface was hardened in about 15 to 20 minutes, and a hydrogel sheet-like gel was formed after 30 minutes. It was able to be peeled off cleanly, and very good result was obtained.

The carbon dioxide external gel was prepared using 0.3 g of granules (X) and 3.0 g of viscous material (Y) of each of the compositions for preparing carbon dioxide external gels of Examples 37 to 40, respectively, and applied to the forearm or the lower thigh. As a result, in all, reaction (evaporation of skin, a feeling of cold, etc.) by absorption of generated carbon dioxide occurred. In addition, each apply | coated carbon dioxide external gel hardened within 30 minutes, and the hydrogel sheet was formed.

The carbon dioxide external gels were prepared using 0.3 g of granules (A) and 3.0 g of viscous materials (B) of the compositions for preparing carbon dioxide external gels of Examples 41 to 59, respectively, and were applied to the forearm or the lower thigh. As a result, in all, reaction (evaporation of skin, a feeling of cold, etc.) by absorption of generated carbon dioxide occurred. In addition, each of the coated carbon dioxide external gels could be applied on the skin mucosa without hardening within 5 minutes after preparation, and the surface hardened in about 15 to 20 minutes, and a hydrogel sheet-like gel was formed after 30 minutes. It could be peeled off cleanly from the skin and very good results were obtained.

The carbon dioxide external gels were prepared using 0.3 g of the granular material (A) and 3.0 g of the viscous material (B) of each of the carbon dioxide external gel preparation compositions of Examples 60 to 69, respectively, and were applied to the forearm or the lower thigh. As a result, in all, reaction (evaporation of skin, a feeling of cold, etc.) by absorption of generated carbon dioxide occurred. In addition, each of the carbon dioxide external gels obtained in Examples 61, 62, and 66 to 69 was hardened within 30 minutes and hydrogel sheeted. On the other hand, each of the carbon dioxide external gels obtained in Examples 60 and 63 to 65 could be applied onto the skin mucosa without curing within 5 minutes after preparation, and the surface hardened in about 15 to 20 minutes, and the hydrogel after 30 minutes. A sheet-like gel was formed, which was then able to be peeled off cleanly from the skin and very good results were obtained.

The carbon dioxide external gels were prepared using 0.2 g of granules (A) and 3.0 g of viscous materials (B) of the compositions for preparing carbon dioxide external gels of Examples 70 to 86, respectively, and applied to the forearm or lower thigh. As a result, in all, reaction (evaporation of skin, a feeling of cold, etc.) by absorption of generated carbon dioxide occurred. In addition, each of the carbon dioxide external gels obtained in Examples 84 and 85 was hardened within 30 minutes and hydrogel sheeted. On the other hand, each of the carbon dioxide external gels obtained in Examples 70 to 83 and 86 could be applied on the skin mucosa without curing within 5 minutes after preparation, and the surface was hardened in about 15 to 20 minutes, and the hydrogel after 30 minutes. A sheet-like gel was formed, which was then able to be peeled off cleanly from the skin and very good results were obtained.

A carbon dioxide external gel was prepared using 0.005 g of a granular material (A) and 3.0 g of a viscous material (B) of the composition for preparing a carbon dioxide external gel of Example 87, and applied to the forearm or the lower thigh. As a result, a reaction (redness of the skin, feeling of cold, etc.) occurred due to absorption of the generated carbon dioxide. In addition, the carbon dioxide external gel obtained in Example 87 was hardened within 30 minutes and hydrogel sheeted.

The carbon dioxide external gel was prepared using 0.05 g of the granular material (A) and 1.0 g of the viscous material (B) of the composition for preparing a carbon dioxide external gel of Example 88 and applied to the forearm or the lower thigh. As a result, a reaction (redness of the skin, feeling of cold, etc.) occurred by absorption of the generated carbon dioxide. In addition, the carbon dioxide external gel obtained in Example 88 was hardened within 30 minutes and hydrogel sheeted.

Evaluation 6: treatment of wounds (2)

About 41-year-old female fingers, a carbon dioxide external gel was prepared and applied using 0.2 g of particulate matter (A) and 3.0 g of viscous material (B) of the composition for preparing carbon dioxide external gel of Example 19. Immediately after preparation, the gel was soft, had good spreadability, and was easy to apply. The feeling of cooling at the application site lasted for 30 minutes or more, and the pain caused by the gap disappeared. The gel was cured appropriately after 30 minutes to form a hydrogel sheet, and thereafter, the gel was protected for 6 hours or more until the sheet was peeled off.

From the above evaluation results, the carbon dioxide external gel obtained by the carbon dioxide external gel preparation composition of the present invention has a stronger cosmetic or medical effect than the kit of Japanese Patent Laid-Open No. 2000-319187 or the composition of WO02 / 80941. It was found that it is obtained in a short time, can be applied thinly and uniformly, and does not flow down when applied, and removal after use is easy.

As described above, according to the first and second carbon dioxide external gel preparation compositions of the present invention, a carbon dioxide external gel in which a large amount of carbon dioxide in a substantially non-bubble state is dissolved in the gel can be obtained. And when this carbon dioxide external gel is used for a skin mucosa, a stronger cosmetic or medical effect can be obtained in a shorter time. For this reason, the desired cosmetic or medical effect can be obtained with less usage and fewer uses. Moreover, since it is a gel, it does not flow down when apply | coated and it is easy to remove after use. Therefore, it can use suitably as external cosmetics, such as cosmetics and a wound coating material.

Claims (17)

It is used for the preparation of carbon dioxide external gel formed by dissolving carbon dioxide in a non-bubble state in a gel. A composition for preparing carbon dioxide external gel, comprising the following granular material (A) and a viscous material (B) mixed with the granular material (A). (A) Granular material which contains a weak acid and a calcium ion trapping agent as an essential component. (B) Calcium carbonate, a gelling agent gelling with calcium ions, and a viscous substance having water as an essential component. The composition for preparing carbon dioxide external gel according to claim 1, wherein the calcium ion trapping agent of the granular material (A) is at least one of sodium ethylenediamine disodium acetate and glycine. The weak acid of the granular material (A) is at least one of sodium dihydrogen phosphate and potassium dihydrogen phosphate, The calcium ion trapping agent of the granular material (A) is at least one of disodium ethylenediamine tetraacetate and glycine, The gelling agent gelled by calcium ions of the viscous substance (B) is sodium alginate, wherein the composition for preparing carbon dioxide for external gels. The composition for preparation of carbon dioxide external gel according to claim 1, wherein the granular material (A) further contains a dispersant. The composition for preparation of carbon dioxide external gel according to claim 1, wherein the granular material (A) further contains a dispersant and a binder. The composition for preparing carbon dioxide external gel according to claim 1, wherein the viscous substance (B) further contains an adhesive for enhancing affinity with the skin mucosa surface. The composition for preparing carbon dioxide external gel according to claim 1, wherein the viscous substance (B) further contains alcohols. The composition for preparing carbon dioxide external gels according to claim 1, wherein the average particle diameter of the granular material (A) is set in a range of 0.05 to 1.0 mm. It is used for the preparation of carbon dioxide external gel formed by dissolving carbon dioxide in a non-bubble state in a gel. A composition for preparing carbon dioxide external gel, comprising the following granular material (X) and a viscous material (Y) mixed with the granular material (X). (X) Granular material which contains weak acid and a dispersing agent as an essential component. (Y) A viscous substance comprising calcium carbonate, a gelling agent gelled with calcium ions, a calcium ion trapping agent, and water as essential ingredients. The composition for preparing a carbon dioxide external gel according to claim 9, wherein the calcium ion trapping agent of the viscous substance (Y) is disodium hydrogen phosphate. The weak acid of the granular material (X) is at least one of sodium dihydrogen phosphate and potassium dihydrogen phosphate, Moreover, the gelling agent which gelatinizes with the calcium ion of the said viscosity substance (Y) is sodium alginate, The composition for preparing carbon dioxide external gel, wherein the calcium ion scavenger of the viscous substance (Y) is disodium hydrogen phosphate. The composition for preparing carbon dioxide external gel according to claim 9, wherein the granular material (X) further contains a binder. The composition for preparing carbon dioxide external gel according to claim 9, wherein the viscous substance (Y) further contains an adhesive for enhancing affinity with the skin mucosa surface. The composition for preparing carbon dioxide external gel according to claim 9, wherein the viscous substance (Y) further contains alcohols. The composition for preparing carbon dioxide external gels according to claim 9, wherein the average particle diameter of the granular material (X) is set in a range of 0.05 to 1.0 mm. A carbon dioxide external gel made by using the composition for preparing carbon dioxide external gel according to any one of claims 1 to 15, wherein carbon dioxide is dissolved in a gel in a non-bubble state. A wound coating material comprising the composition for preparing a carbon dioxide external gel according to any one of claims 1 to 15, wherein carbon dioxide is dissolved in a gel in a non-bubble state.